Salmonella typhimurium

Br J Exp Pathol, 1976 Jun, 57(3), 354 - 60
The effect of T and B lymphocyte depletion on the protection of mice vaccinated with a Gal E mutant of Salmonella typhimurium; Morris JA et al.; Immunosuppressive agents were used to determine the relative importance of T and B lymphocytes in conferring protection to mice vaccinated with a live gal E mutant of Salmonella typhimurium, strain G30D . Lymphocyte transformation and serum agglutination tests showed that while cyclophosphamide (CPA) suppressed B lymphocytes, antilymphocyte sea (ALS) suppressed both T and B cells . The humoral response of vaccinated animals treated with ALS was therefore supplemented by the i.v . injection of serum from untreated vaccinated mice . CPA-treated mice could not control multiplication of the vaccinal strain which eventually killed them . There was little multiplication of the vaccinal strain in the controls and ALS-treated mice, all of which survived to challenge . The vaccinated controls and vaccinated ALS treated groups each survived infection with the challenge strain which was gradually eliminated . It was concluded that humoral immunity was of greater importance than cellular immunity in mice vaccinated i.p . with strain G30D.

Zh Mikrobiol Epidemiol Immunobiol, 1976 Jun, (6), 96 - 9
{Biological properties of Salmonella typhimurium mutants with an altered sensitivity to erythromycin}; Gamaleia NB et al.; S . typhimurium mutants with altered sensitivity to erythromycin (more resistant or more sensitive than the original culture) were selected . Some of the properties of the mutants studied were found to be changed: morphology, character of growth in the liquid nutrient medium with aeration (increased generation time and number of generations in log-period), sensitivity to ionic detergent--sodium dodecyl sulfate (its decrease) . Some of the mutants acquired cross resistance or sensitivity to other antibiotics . The mutants studied had decreased virulence for albino mice . As the mutants were selected by increased resistance or sensitivity to erythromycin, which acted upon the 50 S ribosomal subunits, the pleiotropic changes of their properties were possibly due to some alterations in the ribosomes.

J Gen Microbiol, 1976 Jun, 94(2), 359 - 66
Porphobilinogen-accumulating mutants of Salmonella typhimurium LT2; Sasarman A et al.; Four independent porphobilinogen-accumulating mutants of Salmonella typhimurium LT2 were isolated by selecting for dwarf colony formation on neomycin agar media . Cell-free extracts of the parent strain, but not of the mutants, were able to convert 5-aminolaevulinic acid or porphobilinogen to porphyrins . The results indicated that the mutants were deficient in uroporphyrinogen I synthase (EC . 4.3.I . 8) activity: these are the first mutants of this type reported in S . typhimurium LT2 . Mapping of the hemC locus (for uroporphyrinogen I synthase) by F-mediated conjugation and by P22-mediated transduction showed the gene sequence ilvEDAC-hemC-cya-metE.

Am J Vet Res, 1976 Jun, 37(6), 649 - 55
Influence of antibiotic-supplemented feed on occurrence and persistence of Salmonella typhimurium in experimentally infected swine; Gutzmann F et al.; The effect of chlortetracycline given at a concentration of 220.5 g/metric ton of feed and of a combination product which supplies chlortetracycline (110.2 g/metric ton), sulfamethazine (110.2 g/metric ton), and penicilin G (55.1 g/metric ton) on the occurrence and persistence of Salmonella typhimurium in experimentally infected swine was studied . Weanling pigs (av weight, 8.2 kg) were inoculated via the feed with 10(11) colony-forming units of S typhimurium 298-1NA . An equal number of nonexposed swine given identical treatment were used as controls . Infected pigs had increased temperatures (maximal av, 41 C) for the first 4 days after infection and severe diarrhea during the first 21 days . The use of chlortetracycline and a combination product at subtherapeutic concentrations in feed did not increase the Salmonella pool or prolong the carrier state in swine . A decrease in number of Salmonella shed from swine given chlortetracycline at the concentration of 220.5 g/metric ton was observed . Significant differences did not occur in Salmonella-related deaths or in emergence of multiple antibiotic-resistant Salmonella by antibiotic selection or R factor transfer . Zoonotic transmission of the infecting Salmonella to animal caretakers was not detected.

Proc Natl Acad Sci U S A, 1976 Jun, 73(6), 1882 - 6
Morphogenesis of the bacterial division septum: a new class of septation-defective mutants; Weigand RA et al.; A new class of mutants of Salmonella typhimurium (lkyD mutants) are described . The mutants are defective in morphogenesis of the division septum, and are characterized by a failure of the outer membrane to invaginate despite normal ingrowth of the cytoplasmic membrane and murein layers of the growing septum . The cell envelopes of the mutants show a significant decrease in the bound form of murein-lipoprotein and a corresponding increase in the free form of the lipoprotein . This suggests that the morphogenic defect may result from a defect in formation of covalent bonds between the free lipoprotein of the outer membrane and the murein of the nascent septum.

Proc Natl Acad Sci U S A, 1976 Jun, 73(6), 1877 - 81
Protein-protein interaction in transport: periplasmic histidine-binding protein J interacts with P protein; Ames GF et al.; A component of the high-affinity histidine transport system in Salmonella typhimurium, the periplasmic histidine-binding protein J, interacts with another transport component, the P protein . A mutant J protein, with a defective interaction site but intact histidine-binding site, can function in histidine transport if an appropriate compensating mutation is introduced in the P protein . The interaction between the J and P proteins is an obligatory step in transport . The significance of this interaction and of the involvement of the P protein in multiple transport functions is discussed.

Metabolism, 1976 Jun, 25(6), 615 - 24
Defective lipid disposal mechanisms during bacterial infection in rhesus monkeys; Kaufmann RL et al.; Mechanisms producing hypertriglyceridemia during bacterial sepsis have not been well defined . In this study lipid disposal mechanisms were assessed in 76 infected and 19 control male rhesus monkeys by the ability to dispose of triglycerides after: (1) oral lipid loading; (2) intravenous lipid loading; and (3) by lipolytic enzyme activity tests as measured by postheparin lipolytic activity (PHLA) . Studies were performed both before and 48 hr after intravenous inoculation with either Salmonella typhimurium or Diplococcus pneumoniae when illness was uniformly severe and fasting serum triglyceride elevations were increased maximally . S . typhimurium-infected monkeys demonstrated significant fasting hypertriglyceridemia (p is less than 0.001), reduced clearance of orally and intravenously administered lipid and markedly reduced PHLA . During this gram-negative sepsis, mild lethargy, slight diarrhea, and a 2% mortality were observed . During D . pneumoniae sepsis, average fasting triglyceride concentrations were slightly, but not significantly elevated . While oral lipid clearance was impaired, intravenous lipid clearance was unimpaired, and PHLA was slightly reduced . Marked lethargy, agitation, and a 20% mortality were present during this gram-positive infection . Results of this study support the concept that an impairment of lipid disposal mechanisms, particularly during gram-negative sepsis with S . typhimurium, may significantly contribute to the observed hypertriglyceridemia.

Biochim Biophys Acta, 1976 May 28, 428(3), 647 - 55
Inhibition of growth and aspartokinase activity of Salmonella typhimurium by thialysine; Coles FT et al.; Thialysine (S-2-aminoethyl cysteine) is an analog of lysine and has been reported to inhibit the lysyl-tRNA synthetase activity of Escherichia coli . This analog inhibits the growth of Salmonella typhimurium when added to glucose minimal medium at concentrations of 1.25 mM or greater . The addition of lysine with thialysine restores the normal growth rate, whereas, methionine, valine, or leucine each enhances the growth inhibition casued by thialysine . Enzyme assays demonstrate that thialysine inhibits not only the lysyl-tRNA synthetase from S . typhimurium, but also the aspartokinase activity . Lysine and thialysine appear to inhibit the same 40% of the total aspartokinase because simultaneous addition of the two compounds to the reaction mixture does not increase the inhibition caused by either alone . Furthermore, the slow growth of cells in the presence of 2.5 mM thialysine decreases the level of aspartokinase activity, suggesting that thialysine causes repression of enzyme synthesis as well as inhibition of activity.

Eur J Biochem, 1976 May 17, 65(1), 171 - 6
Histidyl-transfer-ribonucleic-acid synthetase from Salmonella typhimurium . Studies of the sulfhydryl groups; Lepore GC et al.; The reactivity of the sulfhydryl groups of histidyl-t RNA synthetase from Salmonella typhimurium and the effect of substrates on the reactivity has been studied using p-hydroxymercuribenzoate and 5, 5'-dithiobis (2-nitrobenzoic acid) as reagents . It has been found that 5, 5'-dithiobis (2-nitrobenzoic acid) titrates only two sulfhydryl groups per molcule of enzyme and the reaction is essenaitlly monophasic, while p-hydroxymercuribenzoate titrates four sulhydryl groups . As observed kinetically the reaction with p-hydroxymercuribenzoate is strongly biphasic, each phase corresponding to about two sulfhydryl groups per enzyme molecule . With both reagents no detectable difference in sulfhydryl group reactivity was observed when ATP, histidine and tRNA specific for histidine were added individually or in combination to the enzyme . The enzyme activity slowly changes after two or four sulhydryl groups are blocked by 5, 5'-dithiobis (2-nitrobenzoic acid) or p-hydroxymercuribenzoate respectively . A new, stable level of activity is reached that is characterized by a different Km value for the aminoacylation reaction . The results indicate that the sulfhydryl groups reacting with the two reagents used here are neither directly involved in the binding of the substrates nor in the catalytic process . The ultimate change in enzyme activity after reaction of the sulfhydryl groups suggests a transition to an alternative enzyme structure.

Eur J Biochem, 1976 May 17, 65(1), 87 - 94
Enzymic and molecular properties of base-plate parts of bacteriophage P22; Iwashita S et al.; Using 14C-labeled Salmonella bacterial cells as the substrate, the enzymic and molecular properties of the base-plate parts of phage P22 were studied . The base-plate part consisted of a single protein species which cleaved extensively the O-antigen of Salmonella typhimurium, Salmonelly schottmuellerie and with somewhat slower rate that of Salmonella typhi, releasing oligo-saccharide products with rhamnose at the reducing end . Much less cleavage was observed with a strain of S . typhimurium lysogenic for P22, and no significant reaction with Salmonella anatum, Salmonella newington and Salmonella minneapolis . The base-plate part enzyme was a very heat-stable protein and only 10-20% loss was observed after treatment at 85 degrees C for 5 min . The pH optimum of the enzyme was around 7.5, and the glycosidase activity was not influenced by the ionic strength (25-250 mM( of the medium or the presence of Mg2+ . The molecular weight of the base-plate part was 320,000 by sedimentation equilibrium . Dodecylsulphate-acrylamide gel electrophoresis revealed a single band of molecular weight 77,000, indicating that a single base-plate part corresponds to a tetramer of identical subunits . Circular dichroism spectra of P22 base-plate parts showed a major contribution of beta structure . The protein was rich in acidic amino acids, glycine and serine.

J Infect Dis, 1976 May, 133(5), 548 - 55
Hypertriglyceridemia produced by endotoxin: role of impaired triglyceride disposal mechanisms; Kaufmann RL et al.; The role of Salmonella typhimurium endotoxin in producing hypertriglyceridemia was investigated in 70 male rhesus monkeys . Dose-response studies were performed with 0.3-9.0 mg of endotoxin/kg injected intravenously; free fatty acids and triglycerides were measured during the subsequent 8 hr . The effect of endotoxin on lipid disposal mechanisms was assessed by both intravenous lipid-loading tests and total plasma lipolytic activity after administration of heparin . The possible interference of endotoxin with lipid-clearing enzymes was also explored . Smaller doses of endotoxin (0.3 and 0.9 mg/kg) produced significant increments in free fatty acids within 2-5 hr of administration, with minimal trilgyceride increments . Larger doses of endotoxin (2.8-9.0 mg/kg) failed to produce significant elevations in free fatty acids but did result in significant triglyceride increases 2-6 hr after administration . Within 4 hr after administration of 7 mg of endotoxin/kg, both tests showed impaired disposal of lipids . However, once lipid-clearing enzymes were activated, endotoxin did not reduce lipolytic activity in vitro . These results support the contention that endotoxin significantly elevates serum triglyceride concentrations and leads to impaired lipid disposal mechanisms by interfering with the activation of lipid-clearing enzymes.

Cancer Lett, 1976 May, 1(5), 269 - 74
N'-hydroxy-2-aminofluorene: the principal mutagen produced from N-hydroxy-2-acetylaminofluorene by a mammalian supernatant enzyme preparation; Stout DL et al.; A Salmonella typhimurium TA 1538 culture system wasused to monitor the production of mutagen from N-hydroxy-2-acetylaminofluorene by soluble liver enzymes . When benzene was used to extract the mutagen, no mutagenic activity remained in the liver enzyme preparation . The benzene extract contained approximately two-thirds of the total mutagenic activity produced by the liver enzyme preparation . Using thin layer and column chromatography to analyze the benzene extract, we deduced that N-hydroxy-2-aminofluorene accounted for the mutagenic activity which resulted from the incubation of N-hydroxy-2-acetylaminofluorene with soluble liver enzymes.

Am J Vet Res, 1976 May, 37(5), 525 - 9
Effect of lincomycin on prevalence, duration, and quantity of Salmonella typhimurium excreted by swine; DeGeeter MJ et al.; Thirty-one swine (7.5 kg live wt) were fed diets which contained 0 or 110 mg of lincomycin/kg . These pigs were then inoculated with a nalidixic acid-resistant strain of Salmonella typhimurium and monitored for 56 days thereafter to determine (1) the quantity of S typhimurium shed in the feces, (2) the length of time the organism was shed, and (3) the number of swine which shed the organism for the 56-day period after exposure . Addition of lincomycin to diets did not alter these 3 criteria from those obtained in S typhimurium-exposed nontreated swine when results for nontreated and treated swine were compared . In addition, the sensitivity of the S typhimurium strain to 8 antibiotics, 1 nitrofuran, and 1 sulfonamide was not affected by in vivo exposure to lincomycin for 39 days . Lincomycin did not produce adverse effects in either inoculated or noninoculated pigs.

J Bacteriol, 1976 May, 126(2), 634 - 45
Growth rate modulation of four aminoacyl-transfer ribonucleic acid synthetases in enteric bacteria; McKeever WG et al.; The specific activities of arginyl- glutamyl- seryl-, and valyl-transfer ribonucleic acid (tRNA) synthetases were measured in the wild-type and mutant strains of Salmonella typhimurium LT2 and Escherichia coli B/r . In media restricted only by carbon and energy source availability, the specific activities of all four enzymes were proportional to the growth rate, with the exception of seryl-tRNA synthetase in S . typhimurium, which remained essentially constant . Structural gene densities were calculated for these four enzymes and were found not to account for the variation of specific activity with growth rate.

J Bacteriol, 1976 May, 126(2), 823 - 30
Mechanisms of siderophore iron transport in enteric bacteria; Leong J et al.; Uptake of 55Fe- and 3H-labeled siderophores and their chronic analogues have been studied in Salmonella typhimurium LT-2 and Escherichia coli K-12 . In S . typhimurium LT-2, at least two different mechanisms for siderophore iron transport may be operative . Uptake of 55Fe- and 3H-labeled ferrichrome and kinetically inert lambda-cis-chromic {3H}deferriferrichrome by the S . typhimurium LT-2 enb7 mutant, which is defective in the production of its native siderophore, enterobactin, appears to occur by two concurrent mechanisms . The first mechanism is postulated to involve either rapid uptake of iron released from the ferric complex by cellular reduction without penetration of the complex or ligand or dissociation of the complex and simultaneous uptake of both ligand and iron coupled with simultaneous expulsion of the ligand . The second mechanism appears to consist of slower uptake of the intact ferric complex.

Cancer Res, 1976 May, 36(5), 1680 - 5
Shared antigens between bacteria and guinea pig line 10 hepatocarcinoma cells; Minden P et al.; This study was undertaken to investigate the possibility that Listeria monocytogenes, Brucella abortus, and Salmonella typhimurium share antigenic components with guinea pig line 10 hepatocarcinoma cells . Rabbits were immunized with sonicates of these bacteria or line 10 tumor cells . Other rabbits were immunized with line 1 cells, a tumor with antigenic characteristics different from those of line 10 . The binding of antibodies to radiolabeled antigens prepared from extracts of bacteria and line 10 cells was studied by precipitation of radiolabeled antigen-antibody complexes with anti-rabbit immunoglobulin . Antibodies in sera from rabbits immunized with these bacteria and line 10 cells bound both the labeled bacteria and line 10 antigens . Antibodies in sera from rabbits immunized with line 1 cells did not bind the bacterial antigens . Inhibition studies involving reactions between radiolabeled Listeria and line 10 antigens and antibodies to Listeria and line 10 cells confirmed that the binding reactions were specific and that line 10 cells shared antigens with Listeria cells . The possibility that B . abortus and S . typhimurium also shared antigens with line 10 cells was suggested . Whether antigens shared by these bacteria and line 10 cells are identical with tumor-specific antigens was not determined.

Mol Gen Genet, 1976 Apr 23, 145(1), 31 - 6
Occurrence of a regulatory deficiency in purine biosynthesis among pur A mutants of Salmonella typhimurium; Benson CE et al.; A defect in the repression of the de novo purine biosynthetic enzymes was detected among purA mutants of Salmonella typhimurium . We suggest that the defect is caused by an altered purine regulation gene (purR) which affects the response level of at least five of the de novo enzymes to repression by excess adenine . Thus the unlinked genes controlling these enzymes constitute a regulation controlled wholly or in part by a purR gene product . The regulation of the guanine operon is regulated by some other mechanism independent of purR.

Schweiz Med Wochenschr, 1976 Apr 17, 106(16), 543 - 8
{Clarification of a Salmonella typhimurium epidemic in north-eastern Switzerland by means of bacteriological and serological methods}; Pagon S et al.; An outbreak of Salmonella typhi murium caused by person-to-person contacts was observed in Kurhaus (NE Switzerland) in late 1973 . In all, 18 patients with clinical symptoms and 8 asymptomatic carriers were registered . However, 1 1/2 months elapsed before the etiologic diagnosis could be established . The infection was then transmitted, probably by a visiting nurse, to the personnel of a neighbouring school . An outbreak followed thereafter including 31 clinically manifest patients and 10 asymptomatic carriers . Infected food was most probably responsible for the dissemination of the disease, since two asymptomatic carriers were detected among persons engaged in the preparation of food . The close correlation between the two epidemics was confirmed by phague typing of isolated Salmonella strains according to the method of GUINEE . A common Biotype I, Lysotype 650, was identified in all cases . Clinical findings revealed diarrhea in 77,6%, fever in 59,2% and vomiting in 18.4% of cases . Only two patients who were admitted to the hospital, were given chemotherapy . The excretion of Salmonellae in the stools was observed on average for about one month in clinical cases and for 12 days in asymptomatic carriers . All the strains, with one exception, were in vitro sensitive against tetracycline, Chloramphenicol and trimethoprim-sulfamethoxazole . In one case the tetracycline treatment resulted in homologous resistance . In this case the carrier state had been observed for 111 days . Serologic tests were made one month after the outbreak was detected using Widal reactions with antigens of homologous strain . In most patients with clinical symptoms antibody titers were at serum dilutions of more than 1:80, whereas only 4 of the 9 asymptomatic carriers investigated presented with titers in this range . Patients who were not excreting Salmonellae had uniform antibody titers of less than 1:80.

Biochim Biophys Acta, 1976 Apr 16, 433(1), 118 - 32
Outer membrane of Salmonella typhimurium . Transmembrane diffusion of some hydrophobic substances; Nikaido H; The outer membrane, which is composed of lipopolysaccharide, phospholipids, and proteins, is a layer of the cell wall of Gram-negative bacteria, and apparently acts as a penetration barrier for various substances . It had been shown by other workers that "deep rough" mutants of Salmonella typhimurium, whose lipopolysaccharides lack most of the saccharide chains, were much more sensitive than the wild type strain to certain antibiotics and dyes, but not to others . We found that the former group of agents are usually hydrophobic and the latter group mostly hydrophilic . All hydrophilic antibiotics had molecular weights lower than 650, and one of them was shown to diffuse through the outer membrane of 0 degrees C . In contrast, some hydrophobic antibiotics had molecular weights in excess of 1200, and the rate of diffusion of one of them was shown to be extremely dependent both on temperature and on the structure of lipopolysaccharide present . These data and results presented elsewhere suggest, but do not necessarily prove, that most hydrophilic antibiotics diffuse through aqueous pores, whereas hydrophobic antibiotics and dyes mainly penetrate by dissolving into the hydrocarbon interior of the out membrane . In contrast to the outer membrane of deep rough mutants, that of the wild type strain and less defective rough mutants was unusual among biological membranes in that it was practically impermeable to hydrophiobic agents . It is proposed that the difference in hydrophobic permeability between the two types of strains is due to radical differences in the organization of the outer membrane, more specifically to the presence or absence of exposed phospholipid bilayer regions.

J Biol Chem, 1976 Apr 10, 251(7), 2176 - 8
Outer membrane of Salmonella . Isolation of protein complex that produces transmembrane channels; Nakae T; Salmonella typhimurium outer membrane protein complexes can be reconstituted with lipopolysaccharide and phospholipids into membrane vesicles . These vesicles are permeable to a variety of low molecular weight compounds, but not to oligo- and polysaccharides of molecular weight higher than 700 . A protein complex participating in selective membrane permeability can be isolated by gel filtration in the presence of sodium dodecyl sulfate . The active fractions contain three major protein species . The Braun lipoprotein is not associated with this subset of outer membrane proteins.

J Biol Chem, 1976 Apr 10, 251(7), 2023 - 9
A reaction mechanism from steady state kinetic studies for O-acetylserine sulfhydrylase from Salmonella typhimurium LT-2; Cook PF et al.; It has been determined from steady state kinetic studies using the sulfide ion selective electrode that O-acetylserine sulfhydrylase catalyzes a Bi Bi Ping Pong reaction between O-acetyl-L-serine and sulfide . Both O-acetyl-L-serine (OAS) and sulfide exhibit strong competitive substrate inhibition . A fit of all the data to the equation for the mechanism yields KOAS = 0.149 +/- 0.059 mM and KIOAS = 46.91 +/- 10.06 mM for O-acetyl-L-serine and KS2- = 0.066 +/- 0.004 mM and KIS2- = 0.013 +/- 0.006 mM for sulfide . Product inhibition studies varying either substrate at changing fixed levels of cysteine demonstrate that cysteine combines with enzyme at two places along the reaction sequence to produce inhibition with KiCys = 1.048 +/- 0.048 mM and KICys = 11.4 +/- 0.5 mM . Relatively high concentrations of acetate are required to produce inhibition and at least part of the acetate inhibition is due to ionic strength . However, the ability of acetate to reverse the spectral shift produced from the binding of O-acetyl-L-serine to enzyme and the isotope exchange between {14C}acetate and O-acetyl-L-serine does demonstrate that the O-acetyl-L-serine to acetate half-reaction is reversible . There is some doubt as to the specificity of acetate as a product inhibitor, since propionate can also be used to reverse the spectral shift . Spectral studies using ths spectral shift produced from binding O-acetyl-L-serine to enzyme confirms the assignment of a ping-pong mechanism since the spectral intermediate produced is alpha-aminoacrylic acid in Schiff base with pyridoxal phosphate and, therefore, the acetyl moiety has been beta eliminated . Isotope exchange has been demonstrated for both the O-acetyl-L-serine to acetate and sulfide to cysteine half-reactions which also confirms a ping-pong mechanism.

Vet Rec, 1976 Apr 3, 98(14), 276 - 8
Salmonellosis in calves due to lactose fermenting Salmonella typhimurium; Johnston KG et al.; A lactose fermenting strain of Salmonella typhimurium was isolated from two calves which died during an outbreak of acute enteritis . The organism was biochemically typical in all other respects . In one calf, uncomplicated by treatment before death, the autopsy findings were those of a severe fibrinous enteritis which was reproduced in another calf dosed orally with culture . Attention is drawn to scattered reports of lactose fermenting salmonelle causing morbidity and mortality in calves and man.

Infect Immun, 1976 Apr, 13(4), 1069 - 73
Cell-mediated immune response to Salmonella typhimurium infection in mice: development of nonspecific bactericidal activity against Listeria monocytogenes; Zinkernagel RM; Generation of the cell-mediated immune response of CBA/H mice against Salmonella typhimurium (C5S) was monitored by measuring the nonspecifically increased bactericidal activity of macrophages against Listeria monocytogenes . The appearance of detectable levels of macrophage activation was inversely related to the initiating infectious dose . With 3 X 10(3) infecting C5S organisms, significant activity was demonstrable after day 3 . Immunity controlled a challenge with a streptomycin-resistant strain of S . typhimurium (C5R) successfully only by approximately day 7 . In the period of increasing activity against L . monocytogenes, growth of C5R was only delayed . Since such an effect could not be demonstrated in Listeria-infected mice, these findings suggest that immunity against C5R necessitates specific factors besides macrophage activation.

Zentralbl Bakteriol {Orig A}, 1976 Apr, 234(3), 294 - 304
Genetic properties of RM 98, an R plasmid of Salmonella which determines sensitivity to the phage IKe; Khatoon H; An R plasmid of Salmonella, RM98, which determines sensitivity ot the phage IKe (IKeS) and confers resistance to ampicillin (Ap), streptomycin (Sm) and tetracycline (Tc) was studied for its genetic properties in Salmonella typhimurium and Escherichia coli, Transduction of RM98 by P22 in Salmonella yielded transductants of which some had acquired all the recognizable markers (Ap, Sm, Tc, IKeS and resistance transfer factor or RTF) associated with RM98 . This transduction pattern resembles the P22 transduction pattern of IKe-specific R plasmids: R45, R46, R48, R205 and N3 . Preliminary genetic analysis of RM98 has indicated that the determinants of IKeS and RTF are closely linked and the determinants of Ap and Sm are closer to RTF-IKeS than they are to Tc.

Mutat Res, 1976 Apr, 40(2), 73 - 84
Induction of point mutations by different chemical mechanisms in the liver microsomal assay; Herbold B et al.; A selection of chemical agents with different mechanisms of chemical mutability was tested with the liver microsomal assay by using different bacterial tester strains, namely: Salmonella typhimurium TA 1535, TA 1536, TA 1537, TA 1538 and G46 . The tested agents had been selected according to the following criteria . They are all well-known mutagens and can be divided into alkylating agents, anti-metabolites, acridines and those that form radicals in the cell . The mutagens were: dimethylnitrosamine (DMN), diethylnitrosamine (DEN), methyl-nitro-nitrosoguanidine (MNNG), cyclophosphamide, Captan, amethopterine, azathioprine, 6-mecaptopurine, trypaflavine, isoniazide and hydrazine . All except amethopterine gave positive results, showing that this system is very sensitive . In a comparison of the different strains and mutagens we found a correlation between the diameter of the molecule and the permeability of the bacterial cell membrane.

Infect Immun, 1976 Apr, 13(4), 1184 - 92
Evidence for an extrinsic immunogen in effective ribosomal vaccines from Salmonella typhimurium; Hoops P et al.; Previous work has indicated that ribosomes isolated from Salmonella typhimurium were highly immunogenic and afforded excellent protection against homologous challenge . Effective protection was obtained also when ribonucleic acid ( RNA) extracted from these ribosomes was used as a vaccine . In this investigation ribosomes prepared by another method and washed repeatedly in 1 M NH1Cl lost much of their prophylactic potency and yielded poorly protective RNA . The high-salt wash of the ribosomes was immunogenic . The RNA and the protein isolated from the salt wash of the ribosomes were effective vaccines . No intrinsic component of the ribosomes was removed by the NH4Cl wash, since the ability of both "crude" and "clean" ribosomes to function equally well in an in vitro protein synthesizing system was demonstrated . The presence of a component with toxic properties similar to those of endotoxin was found in active vaccines but not in weak ones . This was shown by the ability of effective vaccines to kill lead acetate-sensitized mice and to induce tolerance to endotoxin.

Mutat Res, 1976 Apr, 38(2), 89 - 96
Suppression of dimethylnitrosamine mutagenicity by nitrososarcosine and other nitrosamines; Couch DB et al.; Nitrososarcosine, not mutagenic itself in the host-mediated assay using Salmonella typhimurium G46 as indicator organism, lowered the mutant frequency produced by dimethylnitrosamine (DMN) . Mutant frequency was significantly depressed when 1.0 g/kg nitrososarcosine was administered by gavage 0.5--2.0 h prior to intramuscular injection of 500 mg/kg DMN . Doses of nitrososarcosine as low as 37.2 mg/kg administered 45 min prior to dimethylnitrosamine treatment produced statistically significant reduction of mutant frequency . Dimethylnitrosamine, diethylnitrosamine and dibutylnitrosamine (500 mg/kg) also partially suppressed the mutant frequency produced by 500 mg/kg DMN when administered 45 min prior to dmn . diethylnitrosamine and dibutylnitrosamine were not found to be mutagenic in this test system.

Mutat Res, 1976 Apr, 35(1), 23 - 8
Reaction of nitrosamines in the Udenfriend system: principal products and biological activity; Hsieh ST et al.; Reaction of diethylnitrosamine in the non-enzymatic, ascorbic acid-dependent, hydroxylating system of Udenfriend yielded N-nitroso-2-(ethylamino)-ethanol as the major product extracted into methylene chloride . The major product derived from nitrosopiperidine in the same system was N-nitroso-4-piperidone . These products, however, were mutagenic to Salmonella typhimurium TA 1535 only when activated by a rat liver microsomal preparation.

Appl Environ Microbiol, 1976 Apr, 31(4), 576 - 80
Toxicity and mutagenicity of 2,4,-6-trinitrotoluene and its microbial metabolites; Won WD et al.; TNT (2,4,6-trinitrotoluene) of explosive grade is highly toxic to marine forms that included fresh water unicellular green algae (Selenastrum capricornutum), tidepool copepods (Tigriopus californicus), and oyster larvae (Crassostrea gigas), and mutagenic to Salmonella typhimurium . On the basis of mutagenic assays carried out with a set of histidine-requiring strains of the bacterium, TNT was detected as a frameshift mutagen that significantly accelerates the reversion rate of a frameshift tester, TA-98 . In contrast, the major microbial metabolites of TNT appeared to be nontoxic and nonmutagenic.

Am J Vet Res, 1976 Apr, 37(4), 433 - 7
In vitro and in vivo transfer of drug resistance for Salmonella and Escherichia coli strains in turkeys; Nivas SC et al.; In vitro and in vivo transfers of antibiotic drug resistance were observed when isolates of multi-resistant Salmonella saint-paul and Escherichia coli donors were mated with multi-sensitive E coli and Salmonella typhimurium recipients, respectively . For in vivo studies, day-old turkey poults were used . Drug resistances were transferred either alone or in various combinations . In vitro, transfer was more frequent from E coli to S typhimurium; in vivo, transfer was more often observed from S saint-paul to E coli . Transfer occurred in vivo within 3 or 6 days after the recipient strain was given to poults previously infected with donor bacteria . In some instances, phage typing of S typhimurium indicated a change after transfer of drug resistance from E coli to S typhimurium . The criteria for in vivo transfer of drug resistance were discussed, and the implications of a change in phage type were noted.

J Bacteriol, 1976 Apr, 126(1), 312 - 26
Regulation of purine utilization in bacteria . VI . Characterization of hypoxanthine and guanine uptake into isolated membrane vesicles from Salmonella typhimurium; Jackman LE et al.; Uptake of hypoxanthine and guanine into isolated membrane vesicles of Salmonella typhimurium TR119 was stimulated by 5'-phosphoribosyl-1'-pyrophosphate (PRPP) . For strain proAB47, a mutant that lacks guanine phosphoribosyltransferase, PRPP stimulated uptake of hypoxanthine into membrane vesicles . No PRPP-stimulated uptake of guanine was observed . For strain TR119, guanosine 5'-monophosphate and inosine 5'-monophosphate accumulated intravesicularly when guanine and hypoxanthine, respectively, were used with PRPP as transport substrates . For strain proAB47, IMP accumulated intravesicularly with hypoxanthine and PRPP as transport substrates . For strain TR119, hypoxanthine also accumulated when PRPP was absent . This free hypoxanthine uptake was completely inhibited by N-ethylmaleimide, but the PRPP-stimulated uptake of hypoxanthine was inhibited only 20% by N-ethylmaleimide . Hypoxanthine and guanine phosphoribosyltransferase activity paralleled uptake activity in both strains . But, when proAB47 vesicles were sonically treated to release the enzymes, a three- to sixfold activation of phosphoribosyltransferase molecules occurred . Since proAB47 vessicles lack the guanine phsophoribosyltransferase gene product and since hypoxanthine effectively competes out the phosphoribosylation of guanine by proAB47 vesicles, it was postulated that the hypoxanthine phosphoribosyltransferase gains specificity for both guanine and hypoxanthine when released from the membrane . A group translocation as the major mechanism for the uptake of guanine and hypoxanthine was proposed.

J Virol, 1976 Apr, 18(1), 361 - 4
Role of the bacteriophage P22 tail in the early stages of infection; Israel V; The initial binding of phage P22 to its host, Salmonella typhimurium, is dependent in a linear fashion on the number of tail parts per phage head . (The normal head has six.) There is also a later step which depends on tail parts . This step must occur some time after hydrolysis of the O antigen has been initiated and before ejection of phage DNA from the head is complete . This step causes PFU to depend on approximately the third power of the number of tail parts per head.

Mutat Res, 1976 Apr, 38(2), 81 - 8
Vinyl chloride dependent mutagensis: effects of liver extracts and free radicals; Garro AJ et al.; The mutagenic effects of vinyl chloride (VC) on Salmonella typhimurium strain TA1530 are enhanced by mouse or rat liver extracts . The extracts prepared from mice pretreated either with vinyl chloride or the microsomal enzyme inducer, Aroclor 1254, did not produce any greater stimulation of VC-dependent mutagenesis than extracts from untreated animals . These same extracts, however, differed markedly in their capacity to stimulate the mutagenicity of dimethylnitrosamine (DMN), a compound which is converted to a mutagen by an NADPH dependent microsomal mixed function oxidase . The order of activity of the extracts with DMN was Aroclor pretreated is greater than untreated is greater than VC pretreated . Furthermore, the stimulatory effect of the liver extracts on VC mediated mutagenesis did not require NADPH and was still evident in liver extracts in which the microsomal mixed function oxidase system had been heat inactivated . The mutagenic activity of VC also was found to be stimulated by riboflavin in the presence of light suggesting that free radicals may be involved in VC dependent mutagenesis.

Mol Gen Genet, 1976 Mar 22, 144(2), 199 - 204
Site c27 in phage P22 and control of the pathway to lysogeny; Tokuno S et al.; Phage P22 mutation c27 defines a site required for establishment , but not maintenance of repressor synthesis . This study confirms that P22 c27 is able to synthesize repressor if active repressor is present . An interaction involving gene products of c1 and c3 and the site c27 retards expression of the lytic genes of P22 . Mutations in gene c1 eliminate the retardation of lytic gene expression, but c27 does not alleviate the retardation . These results are used to construct a model that postulates that binding of c1 and c3 products to DNA at or near c27 is sufficient to cause retardation of lytic gene expression . The functioning of c27 is contrasted to that of the analogous cy mutants of lambda . The effect of the c27 mutation upon alleviation of "cl repression" was studied in a partial revertant of Salmonella typhimurium Pox-1 in which c1 repression is exaggerated . The higher frequency of lysogenization seen in the mutant host is related to enhanced cl repression.

J Bacteriol, 1976 Mar, 125(3), 1005 - 12
Effect of methionine on chemotaxis by Bacillus subtilis; Ordal GW; Bacillus subtilis, like Escherichia coli and Salmonella typhimurium, carries out chemotaxis by modulating the relative frequency of smooth swimming and tumbling . Like these enteric bacteria, methionine auxotrophs starved for methionine show an abnormally long-period of smooth swimming after addition of attractant . This "hypersensitive" state requires an hour of starvation for its genesis, which can be hastened by including alanine, a strong attractant, in starvation medium . Susceptibility to repellent, which causes transient tumbling when added, if anything, increases slightly by starvation for methionine . The results are interpreted by postulating the existence of a methionine-derived structure that hastens recovery of attractant-stimulated bacteria back to normal.

Tsitol Genet, 1976 Mar-Apr, 10(2), 99 - 102
{Mutagenic activity of benzonal}; Fonshtein LM et al.; Benzonalum mutagenic activity was demonstrated in a dominant lethal test on mice . The late spermatids stage proved to be the most sensitive in this respect . The benzonalum did not evoke any cytogenetic activity, that was shown by counting chromosome aberrations in metaphases of the bone marrow cells in vivo and did not induce gene mutations in tester trains of Salmonella typhimurium in vitro and in vivo (a host-mediated assay).

Am J Vet Res, 1976 Mar, 37(3), 345 - 7
Effect of resistance possessed by certain enteric microorganisms upon orally inoculated Salmonella; Hooper DG et al.; Mice shedding aerobic gram-negative microorganisms with high levels of resistance to tetracycline were orally inoculated with Salmonella typhimurium . Levels of resistance of salmonella isolated from tissue were shown not to be increased and, in most instances, were lower than preinoculation levels.

J Bacteriol, 1976 Mar, 125(3), 892 - 904
Biosynthesis and assembly of envelope lipoprotein in a glycerol-requiring mutant of Salmonella typhimurium; Lin JJ et al.; A glycerol-requiring mutant of Salmonella typhimurium was used in a study of the biosynthesis and assembly of a structural lipoprotein in the cell envelope of gram-negative bacteria . Upon removal of glycerol from the growth medium, the biosynthesis of lipoprotein, as measured by radioactive arginine incorporation, was reduced by the same extent as that of other envelope proteins, the cumulative incorporation of arginine being 20% of that of the unstarved control cells . However, the incorporation of radioactive palmitate into lipoprotein was more severely curtailed after glycerol starvation, the cumulative rate of which was 8% of that observed in the unstarved cells . It was further observed that the lipoprotein synthesized in the glycerol-starved cells was more enriched in unmodified cysteine, which is known to be the N-terminal amino acid of lipoprotein, than that synthesized in the unstarved cells . We conclude that the synthesis of the apoprotein portion of Braun's lipoprotein proceeds independently of the attachment of diglyceride to the sulfhydryl group of the N-terminal cysteine and may, in fact, precede the incorporation of the diglyceride moiety.

Chem Biol Interact, 1976 Mar, 12(3-4), 251 - 63
The mutagenicity of chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid, conceivable metabolites of vinyl chloride; Rannug U et al.; Previous investigations have shown that the carcinogen vinyl chloride causes base-pair substitution in the bacterium Salmonella typhimurium . The ability of four conceivable metabolites-chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid-to cause base-pair substitution directly in Salmonella typhimurium TA1535 has been compared . The main comparison was performed at initial concentrations from 0.1 to 1.5 mM . In this region, however, a mutagenic effect was observed only with chloroethylene oxide and chloroacetaldehyde, the former being approximately 20 times more effective than the aldehyde when compared on a molar basis.2-Chloroethanol and chloroacetic acid were studied also at higher concentration (1 mM-1 M), and a weak mutagenic response was found with 1 M 2-chloroethanol solution . With chloroacetic acid no enhancement of the mutation frequency could be detected . Chloroethylene oxide was found to be approximately 450 times more effective as a mutagen than chloroacetaldehyde when the comparison is based on exposure doses, defined as the time-dependent concentrations of the compounds in the treatment solutions, integrated between the times of onset and termination of treatment . Similarly, chloroethylene oxide was 10,000-15,000 times more effective as a mutagen than ethylene oxide, used as a positive control.

Infect Immun, 1976 Mar, 13(3), 800 - 7
Nonspecific bactericidal activity of the lactoperoxidases-thiocyanate-hydrogen peroxide system of milk against Escherichia coli and some gram-negative pathogens; Reiter B et al.; Two strains of Escherichia coli and one strain each of Salmonella typhimurium and Pseudomonas aeruginosa were killed by the bactericidal activity of the lactoperoxidase-thiocyanate-hydrogen peroxide system in milk and in a synthetic medium . H2O2 was supplied exogenously by glucose oxidase, and glucose was produced at a level which was itself noninhibitory . Two phases were distinguished: the first phase was dependent on the oxidation of SCN(-) by lactoperoxidase and H2O2, which was reversed by reducing agent, and the second phase was dependent on the presence of accumulated H2O2, which was reversed by catalase . The latter enzyme could also reverse the first phase, but only when present in excessive and unphysiological levels . The bactericidal activity was greatest at pH 5 and below, and it depended on the SCN(-)concentration and on the number of organisms . Since raw or heated milk neutralizes the acid barrier against infection in the stomach, the bactericidal system discussed may contribute to the prevention of enteric infections in neonates.

J Bacteriol, 1976 Mar, 125(3), 1105 - 11
Transduction of chromosomal genes between enteric bacteria by bacteriophage P1; Tyler BM et al.; We have used P1 transduction to create intergeneric hybrid strains of enteric bacteria by moving the genA and hut genes between Klebsiella aerogenes, Escherichia coli and Salmonella typhimurium . The use of E . coli as the recipient in such transductions permits the construction of episomes and specialized transducing phage containing non-E . coli material . The effect of host restriction modification and deoxyribonucleic acid homology on the frequency of intergeneric transduction of these loci has been examined.

Mol Gen Genet, 1976 Feb 27, 144(1), 87 - 95
The synthesis of S-adenosylmethionine by mutants with defects in S-adenosylmethionine synthetase; Hobson AC; Some metK mutants of Salmonella typhimurium with constitutive methionine biosynthesis have no detectable S-adenosylmethionine (SAM) synthetase, the enzyme which converts methionine to SAM, the postulated corepressor of the methionine pathway . However, these mutants are not auxotrophic for SAM, an essential compound for many reactions.

Science, 1976 Feb 27, 191(4229), 868 - 9
Mutagenicity of malonaldehyde, a decomposition product of peroxidized polyunsaturated fatty acids; Mukai FH et al.; Incubation of histidine requiring auxotrophs of the bacterium Salmonella typhimurium with malonaldehyde, a three-carbon dialdehyde, produced an increased number of revertants in specific strains . Mutagenesis was only observed in frameshift mutants with normal excision repair and did not occur in those base-pair substitution mutants tested . The results are consistent with the cross-linking of bacterial DNA by malonaldehyde leading to mutagenesis expressed through the error-prone repair system.

Mol Gen Genet, 1976 Feb 27, 144(1), 97 - 105
Envelope mutation promoting autolysis in Salmonella typhimurium; Anton DN et al.; Two strains independently isolated in Salmonella typhimurium display abnormal autolytic activity when nutrient broth becomes alkaline . They also show increased sensitivity to deoxycholate, EDTA, and sodium dodecyl sulfate . Response to acridine orange remains normal . In both strains a single stable mutation is responsible for all the changes . The same gene, called envD, appears to be involved in both mutant strains . envD has been located at minute 33 of the Salmonella genetic map, between markers sucA and nadA, very close to the latter . envD also affects morphological characteristics of the cells . Many mutant cells are shorter than wild type bacteria, and appear frequently associated in short chains of 4 to 10 cells . Furthermore, envD mutants display division by septation under conditions that preclude its observation in wild type strains.

J Biol Chem, 1976 Feb 25, 251(4), 1052 - 6
Transport and metabolism of vitamin B6 in Salmonella typhimurium LT2; Mulligan JH et al.; Salmonella typhimurium LT2 concentrates radioactivity intracellularly from {3H}pyridoxal or {3H}pyridoxine up to 25 times the external concentration . After 1 min of uptake intracellular radioactivity is found as phosphorylated vitamin B6 . The process is sensitive to temperature and is maximally active at pH 8.1, but under the conditions tested it is insensitive to monovalent cations or metabolic inhibitors, and does not require an exogenous energy source . The Km values for uptake of pyridoxine and pyridoxal are 2.0 x 10(-7) M and 1.2 x 10(-7) M, respectively; {3H}pyridoxamine is not transported . Evidence is presented for an uptake mechanism involving facilitated diffusion followed by trapping by pyridoxal kinase . S . typhimurium also appears to lack a periplasmic binding protein for vitamin B6.

Eur J Biochem, 1976 Feb 16, 62(2), 293 - 8
Histidyl transfer ribonucleic acid synthetase from Salmonella typhimurium . Interaction with substrates and ATP analogues; Di Natale P et al.; Structural requirements for substrate binding to histidyl-tRNA synthetase from Salmonella typhimurium have been investigated using ATP analogues . Ki values and the relative binding affinity of the enzyme for these analogues have been determined in the tRNA aminoacylation reaction . The enzyme is highly specific for ATP: no binding was found for GTP, CTP, TTP and UTP . dATP is a very poor substrate for acylation of tRNA, with a Km 40-fold higher than that of ATP . Binding of adenosine 5'-triphosphate requires interactions of the amino group of adenosine and the sugar moiety; the 2' and the 5' positions of the ribose appear to be essential for recognition; the phosphate groups enhance the binding . AMP is a noncompetitive inhibitor with ATP . The interaction of histidyl-tRNA synthetase, a dimeric enzyme, with histidine and ATP was examined by fluorescence measurements at equilibrium and by equilibrium dialysis . Binding with L-histidine is significantly tighter at pH 6 than at pH 7, while the ATP binding is independent of pH . The stoichiometry was measured at pH 6 than at pH 7, while the ATP binding is independent of pH . The stoichiometry was measured at pH 7.5 by equilibrium dialysis and is 1 mol ATP/mol enzyme and, variably, close to 2 or 1 mol histidine/mol enzyme.

Vet Rec, 1976 Feb 14, 98(7), 126 - 30
An outbreak of S typhimurium in sheep and its consequences; Hunter AG et al.; An outbreak of Salmonella typhimurium in an upland sheep flock was characterised by rapid spread and heavy mortalities in ewes and young lambs . Clinical signs included diarrhoea and abortion . Abomasitis was the most striking and consistent post mortem lesion . Vaccination was the only control method that was apparently successful . Infection also occurred in the cattle, farm personnel, and a dog . Following the outbreak, pasture contamination and excreting cattle provided a reservoir of infection so that contamination of water courses and sporadic cases occurred over a year later.

J Hyg (Lond), 1976 Feb, 76(1), 97 - 108
The virulence of trimethoprim-resistant thymine-requiring strains of Salmonella; Smith HW et al.; A thymine-requiring (thy-), trimethoprim-resistant (tmpr) mutant isolated from the faeces of chickens experimentally infected with salmonella typhimurium and treated with mixture of trimethoprim and sulphadiazine was less virulent for chickens than the parent strain and a thy+tmps revertant prepared in vitro from the mutant . The difference in chicken-virulence was more noticeable when the strains were administered orally than when they were administered subcutaneously . All tmpr mutants prepared in vitro from four other salmonella strains were also thy-; those tested were less virulent for chickens and mice than their parent strains . After oral infection, thy- salmonella organisms were found much less commonly in the alimentary tract of chickens then were thy+ organisms . This was especially so in the caeca, the principal site of colonization of both the thy+ and thy- organisms . Relatiely high concentrations of thymine or related compounds were found in the contents of all regions of the alimentary tract of chickens except the caeca; the caeca usually contained low or undetectable concentrations . The thy- salmonella strains would not grow on one brand of briliant green agar because of its deficiency in thymine; their colonial and appearance on other kinds of media used for isolating salmonellae from clinical material was often 'un-salmonella-like'.

J Hyg (Lond), 1976 Feb, 76(1), 41 - 7
Survival of Salmonella east bourne and Salmonella typhimurium in chocolate; Tamminga SK et al.; Experiments were carried out to assess the reduction rate of two salmonella strains (S . eastbourne and S . typhimurium) in chocolate bars . After artificial contamination of chocolate, after 'conching', with about 10(6) S . eastbourne/g . this organism was still recovered after 9 months storage . The strain of S . typhimurium was less resistant . Both serotypes died off more rapidly in bitter chocolate than in milk chocolate . After contamination with a smaller dose (about 10(3)/g.) with these two serotypes, similar differences were observed.

Infect Immun, 1976 Feb, 13(2), 470 - 4
Role of plasma filtration in the intestinal fluid secretion mediated by infection with Salmonella typhimurium; Giannella RA et al.; The mechanisms whereby invasive enteropathogens, e.g., Salmonella typhimurium, induce intestinal secretion are largely unknown . Since these organisms penetrate the intestinal epithelium, disrupt the brush border, and evoke an acute inflammatory reaction, increased plasma filtration through a damaged, more permeable epithelium might contribute to the secretory process . To examine this possibility, the plasma-to-lumen clearance of two different sized molecules, {51Cr}albumin and {14C}mannitol, was measured in the in vivo rabbit ileal loop and in vivo rhesus monkey models of salmonellosis . In the rabbit ileal loop model, the clearance of neither molecule was increased when compared to cholera toxin-exposed loops . In the rhesus monkey, clearance of {14C}mannitol into the jejunum, ileum, and colon of Salmonella-infected animals did not differ from the observed in control animals . These data indicate that invasion of the intestinal mucosa by S . typhimurium has not substantially altered the permeability characteristics of the intestinal mucosa and that plasma filtration through a damaged, more permeable mucosa does not contribute to the Salmonella-induced intestinal secretory process.

Chem Biol Interact, 1976 Feb, 12(2), 121 - 34
On the mode of action of 5-diazouracil on bacterial cell division; Coates DA et al.; Cell division by strains of Escherichia coli and Salmonella typhimurium is inhibited by 5-diazouracil (5-DU) . Division recovers in the presence of the inhibitor after a period which is temperature-dependent . Recovery is probably due to breakdown of 5-DU and the rate of this breakdown is apparently increased at alkaline pH . Growth with 5-DU caused only a slight reduction in the rate of murein synthesis and no alteration in the properties or composition of membranes of S . typhimurium . The agent caused chaining in Streptococcus fecalis and inhibition of the penicillin-induced lysis of S . typhimurium . These effects may have been due to direct inhibition of lysin activity but an indirect effect seems more likely . The most marked effect of 5-DU on S . typhimurium was to cause a transient inhibition of DNA synthesis . Since 5-DU did not stop uncoupled cell division (i.e . division occurring independently of DNA replication) and since lon- strains were more sensitive to 5-DU than lon+ strains, it was concluded that 5-DU acts on cell division via an inhibitory effect on DNA replication.

J Trop Med Hyg, 1976 Feb, 79(2), 28 - 31
Relation between Salmonella typhimurium biotypes and drug resistance, Teheran, Iran (1962-1973); Badalian K et al.; According to the procedure of Cordano (1971), the identification of biotypes of 118 strains of Salmonella typhimurium isolated from stools or rectal swabs of patients with sporadic cases of diarrhoea on the Central Plateau during the period 1962-1973 revealed that: From 118 S . typhimurium, 65 (55-1%) were biotype "d", 50 (42-4%) were "a" and three (2-5%) were "b" . The predominant biotype was "d", followed by the "a" biotype, and "b" was rarely encountered . Biotype "d" has existed since 1965, and after that date has increased . Biotype "a" existed from the beginning of the study, but has decreased during the period 1962-1973 . Sensitivity tests were performed according to Bauer (1966) . Biotypes "d" and "a" showed a high degree of resistance to tetracycline, chloramphenicol, streptomycin, triple-sulfa, ampicillin, furazolidone, kanamycin, neomycin, paromomycin, cephalothin and co-trimoxazole . All isolated biotypes "d" were multiple drug-resistant, while some of the strains of biotype "a" were resistant and some sensitive . All three biotypes "b" were sensitive to all drugs examined . Resistance to drugs for biotypes "d" and "a" increased with time . The predominant pattern of resistance for all biotypes was found to be resistance to eight drugs: tetracycline, chloramphenicol, streptomycin, triple-sulfa, ampicillin, kanamycin, neomycin and paromomycin (Tc, Cm, Sm, Su, Am, K, N, Par) . Considering the relationship between resistance pattern and biotypes, the predominant pattern in biotype "d" was resistance to eight drugs (Tc, Cm, Sm, Su, Am, K, N, Par) (47-7%), and in biotype "a" was resistance to nine drugs, tetracycline, chloramphenicol, streptomycin, triple-sulfa, ampicillin, furazolidone, kanamycin, neomycin, paromomycin (Tc, Cm, Sm, Su, Am, Fx, K, N, Par) (28%).

Zh Mikrobiol Epidemiol Immunobiol, 1976 Feb, (2), 78 - 81
{Study of mutants of Salmonella typhimurium with altered sensitivity to the antibiotic fusidin}; Gamaleia NB et al.; S . typhimurium mutants with altered sensitivity to fusidic acid (more resistant or more sensitive than the original culture) were selected . The mutants studied changed some of their properties (morphology, antigenic structure, and biochemical activity) . They were characterized by a lower growth rate and probably by some alterations in the envelope cell structures- Some mutants acquired cross resistance or sensitivity to other antibiotics . As the mutants were selected by increased resistance or sensitivity to fusidic acid which affected the translocation factor G of the ribosome cycle, such pleiotropic changes of their properties could be due to some alterations in the G-factor itself.

J Gen Microbiol, 1976 Feb, 92(2), 311 - 24
Genetic transfer of Salmonella O antigens to Escherichia coli O8; Kiefer W et al.; His+ hybrids from a cross between a Salmonella typhimurium donor and an Escherichia coli O8 recipient expressed E . coli O8 specificity and in addition Salmonella O4,12-specificity . This indicated that the recipients had received the his-linked donor rfb cluster determining the synthesis of S . typhimurium O-specific repeat units and that the rfb genes of both mating partners are functional in these hybrids . Chemical analyses showed that the hybrids contained an E . coli O8 lipopolysaccharide (O antigen) and a S . typhimurium specific lipopolysaccharide with only one O-specific repeat unit (SR antigen) . O8-negative mutants selected from the O8-positive hybrids retained the Salmonella O-specificity and represent semi-rough (SR) forms, because the rfc gene(s) determining the polymerization of repeat units has not been transferred . Attempts to introduce the S . typhimurium rfc locus into E . coli O8 remained unsuccessful . Crosses between a S . typhi donor and E . coli O8 gave rise to smooth (S) and SR His+ recombinants exhibiting only S . typhi O-specificity . The smooth recombinants are assumed to have obtained the his-linked rfb cluster and in addition the rfc gene(s) of the donor . The exchange of the rfb region of such smooth recombinants by that of a S . typhimurium donor led to smooth hybrids with O4,(5), 12-specificity . The phenotypically smooth recombinants exhibited concomitantly S- and SR-lipopolysaccharides of S . typhi and S . typhimurium O-specificity, respectively.

Eur J Biochem, 1976 Jan 15, 61(2), 377 - 86
Purine-nucleoside phosphorylase from Salmonella typhimurium and Escherichia coli . Initial velocity kinetics, ligand banding, and reaction mechanism; Jensen KF; Purine nucleoside phosphorylase from Salmonella typhimurium has been subjected to kinetic analysis i.e . determination of initial velocity patterns and product inhibition studies . The kinetic results suggest that the enzyme works by a sequential reaction mechanism, where the nucleoside, phosphate, and pentose 1-phosphate are all able to bind to the free enzyme, whereas it appears that the purine base binds after addition of the pentose 1-phosphate . The proposed mechanism is confirmed by substrate binding studies . In addition to the enzyme-substrate complexes suggested by the kinetics, the binding studies revealed a 'dead end' complex, consisting of enzyme, phosphate, and purine base . Similar binding experiments were carried out using the enzyme from Escherichia coli . The results suggest that this enzyme works by an identical reaction mechanism . The binding data are in agreement with the presence of six binding sites per native enzyme molecule, one binding site per subunit, for each ligand . Both enzymes show normal Michaelis-Menten kinetics for their substrates with the exception of phosphate, for which the double-reciprocal plots are concave down . This behaviour is seen in both binding and velocity curves, and most likely is a result of negative cooperativity in the binding of phosphate to the enzyme.

Am J Public Health, 1976 Jan, 66(1), 82 - 3
Canine salmonellosis: A review and report of dog to child transmission of Salmonella enteritidis; Morse EV et al.; Dogs have been shown to harbor 53 salmonellae serotypes . Multiple simultaneous infections with 2 to 4 serotypes have been observed . The prevalence of canine salmonellosis may be a high as 27 per cent . Salmonella typhimurium and S . anatum are the most common etiologic agents . Dogs commonly experience a sub-clinical course of salmonellosis . Some investigators state that the dog may serve as a source of human infections . A few reports in the literature have documented this fact . The transmissions of S . enteritidis from dog to child is described in this article.

J Infect Dis, 1976 Jan, 133(1), 72 - 8
Genetics of resistance to infection with Salmonella typhimurium in mice; Plant J et al.; Eight strains of inbred mice fell into two sharply defined groups . Four strains (CBA, A/JAX, C3H/He, and DBA/2) were resistant (LD50, greater than 10(5)) to Salmonella typhimurium C5 given subcutaneously . The other four strains (Balb/c, C57BL, B10.D2 {new line}, and DBA/1) were susceptible (LD50, less than 10) . No intermediate resistance was seen . Examination of the F1, F2, and parental backcross generations bred from matings of CBA and Balb/c mice showed that resistance behaved as a simple Mendelian dominant . Resistance was not linked to H-2 genes, and no useful marker has yet been found . However, as previously demonstrated in the parent strains, resistance in the hybrids was related to the ability to produce a good delayed-type hypersensitivity reaction to an extract of S . typhimurium.

J Bacteriol, 1976 Jan, 125(1), 94 - 101
Regulatory mutants and control of cysteine biosynthetic enzymes in Salmonella typhimurium; Borum PR et al.; The cysB region in Salmonella typhimurium regulates in a positive manner the noncontiguous structural genes for the enzymes responsible for sulfate reduction in cysteine biosynthesis . We treated three cysB mutants with chemical mutagens and selected 81 secondary mutants in which the inability to utilize sulfate was suppressed . Growth experiments on the suppressed mutants showed that the original loss of sulfate utilization had been corrected to varying degrees and that portions of the pathway had been established in abnormal relationship to one another . Sixty of the suppressed mutations were mapped via transductional analysis, and each was very closely linked to the original cysB mutation . We demonstrated that the cysB product functions in the regulation of the cysteine biosynthetic enzymes during both logarithmic growth and stationary phase . Mutation can alter the regulatory response of one enzyme in either an upward or downward direction while the regulation of other enzymes in the pathway remains unchanged . These data are consistent with the idea of a multivalent or multisite regulator molecule.

Mutat Res, 1976 Jan, 40(1), 19 - 30
Mutagenicity screening of pesticides in the microbial system; Shirasu Y et al.; A survey on the mutation induction capacity was made in the microbial system on 166 pesticides including 57 fungicides, 63 herbicides and 46 insecticides . The screening methods consisted of the rec-assay procedure, a sensitivity test utilizing H17 Rec+ and M45 Rec- strains of Bacillus subtilis, as well as the reversion assays on plates utilizing auxotrophic strains of Escherichia coli (WP2) and Salmonella typhimurium (Ames series) . Chemicals inducing reversions were detected only among those showing positive effects in the rec-assay but not among negative samples . In addition to Captafol, Captan, Dexon and NBT of which mutagenicities have been previously reported, Dichlorvos, Folpet, 2-hydrazinoethanol (HEH), 5-nitro-1-naphthonitrile (NNN) and Vamidothion were found to be mutagens in our systems.

J Bacteriol, 1976 Jan, 125(1), 340 - 5
Genetic and physiological classification of periplasmic-leaky mutants of Salmonella typhimurium; Weigand RA et al.; Mutants of Salmonella typhimurium that leaked periplasmic proteins were isolated . Four classes of mutants were identified by their increased sensitivity to dyes, detergents, or antibiotics . Conjugation studies indicated that representatives of two classes mapped in the proA-galE region of the Salmonella chromosome and two in the cysI-argE region . According to their bacteriophage sensitivity pattern, all four of the mutant classes appear to retain the smooth lipopolysaccharide characteristic . One class of mutants has an abnormal cell envelope in which the outer membrane balloons away from the murein layer.

Microbios, 1976, 17(68-69), 93 - 131
Effect of chemical modification by (di)imidoesters on cells and cell envelope components of Escherichia coli and Salmonella typhimurium; Schmalreck AF et al.; Cells and cell envelope components of Escherichia coli and Salmonella typhimurium were treated with mono- and bifunctional imidates like methylbutyrimidate, methyl-4-mercaptobutyrimidate and dimethylsuberimidate, and after determination of the appropriate conditions, the effects on structure and function were investigated . Within 10 min after treatment of the bacteria with 5 mM of the (di)imidoesters, active transport, DNA-, RNA-, protein- and lipid-synthesis were severely inhibited . After crosslinking, cell envelope components, e.g . phospholipids, lipopolysaccharide, and periplasmic proteins, became partly inextractable . Crosslinked cells showed increased resistance to ultrasonic treatment and osmotic or detergent induced lysis . By the reaction of (di)imidoesters with phospholipids containing no amino groups, it could be demonstrated that non-amidine products were also formed . In addition, freeze-fracturing and freeze-etching demonstrated distinct crosslinked areas in the cell envelope of E . coli B.

Microbios, 1976, 16(64), 81 - 90
Localization of the protective antigen in Salmonella typhimurium; Mates A et al.; Active protection to challenge with 100 LD50 of Salmonella typhimurium could be induced in white mice by inoculation with 10(3) live bacteria (0.1 LD50) or 10(8) heat killed bacteria (56 degrees C for 30 min), or 20 gamma ribosomal fraction . Passive protection could be given by antisera taken from hyperimmune rabbits inoculated with either the heat killed bacteria or by the ribosomal fraction . No direct correlation between antibody titre to 'O' antigen and degree of protection was observed . Absorption of any antisera with 'O' antigen decreases its protective power . The protective antibodies could be completely absorbed from both antisera by heat killed bacteria and released afterwards . Abosrption of 'O' antibodies from this preparation decreases the ability of the mice to survive the challenge . Our data suggests that the antigens which induce protective antibodies are located on the surface of the bacteria . The protection achieved by this antisera is probably the result of a synergistic effect between the antibodies to the 'O' antigen and other antigen(s).

Arch Invest Med (Mex), 1976, 7(3), 127 - 34
{Ribosomal vaccine obtained from Salmonella typhimurium and tested against the challenge of an orally administered virulent microorganism}; Molinari JL et al.; Ribosomal preparation obtained from Salmonella typhimurium, used as a vaccine, was able to induce protection of 100% on mice challenged with 5.5 X 10(9) CFU of S . typhimirium administered by oral route . Effective dose at 50% was of 0.1085 mug, expressed as ribonucleic acid (RNA) . This vaccine induced an important humoral response as soon as in nine days . The ribosomal preparation used in this work was maintained at 4 degrees C at least for eighty two days . This fact shows an adequate stability of this biological product.

Vet Med Nauki, 1976, 13(7), 16 - 24
{Dynamics of agglutination in birds artificially infected with Salmonella gallinarum-pullorum and Salmonella typhimurium and treated with sulfaguanidine and furazolidone}; Canovska MKh; Canadian Leghorn chickens were used to study the effect of sulfaguanidine and furazolidon on the dynamics of blood agglutinin formation . The birds were artificially infected with Salmonella gallinarum-pullorum and Salmonella typhimurium . At various intervals following infection they were treated with sulfaguanidine 1% tablets and 0.04% furazolidon . The level of agglutinins was determined by the methods of Huddleson (whole blood agglutination reaction), the fast serum agglutination, the method after Wright, and the indirect hemagglutination reaction . It was found that the agglutinin level in birds treated in the course of ten days with the chemotherapeutics mentioned prior to their infection did not change . The use of these chemotherapeutics parallel to the infection of the test birds and ten days later inhibited agglutinin formation . This was more pronouncedly expressed in birds treated with furazolidon . The delayed use of these therapeutic means did not inhibit substantially the level of blood agglutinins.

Microbios, 1976, 15(61-62), 221 - 8
Identification of an antibody binding site in the phase-1 flagellar protein of Salmonella typhimurium; Joys TM; A synthesized pentapeptide equivalent to a region of the phase-1 flagellar protein of Salmonella typhimurium was found to be specifically bound by antisera possessing agglutinating activity against the phase-1 flagellar antigen i.

Can J Comp Med, 1976 Jan, 40(1), 80 - 8
The significance of the serotype in the clinical and pathological features of naturally occurring porcine salmonellosis; Wilcock BP et al.; Salmonellosis was the diagnosis in 63 of 327 consecutive porcine necropsy accessions during a one year period in Indiana, an incidence four to ten times that previously reported in other areas . A herd outbreak was usually either a septicemic disease characterized by sudden mortality . Little overlap between these two syndromes were seen . Animals dying with the septicemic form usually yielded Salmonella choleraesuis var . kunzendorf on culture . Salmonella typhimurium was the usual isolate from cases of enteric salmonellosis . Oral inoculation of SPF pigs with S . typhimurium resulted in a disease similar to naturally occurring enteric salmonellosis . The pathology of porcine salmonellosis due to S . typhimurium is described.

Genetika, 1976, 12(5), 149 - 56
{Differences in the mutagenic effectiveness of N-nitrosomethyl- and N-nitrosoethylurea acting on bacterial DNA in vivo}; Vasil'eva SV; Chemically induced lethals and reversion frequencies of two mutants of Salmonella typhimurium LT-2 1530 and 1532 were examined . Prototrophic mutants to histidine independence occurred by two different mechanisms and were induced by nitrous acid, hydroxylamine, N-nitrosomethylurea (NMU), N-nitrosoethylurea (NEU) and N, N, nitrosodimethylurea (NDMU) . The ability of the mutants to revert was affected by the chemical structure (in the row of N-nitrosoalkylurea - by alkyl group) of the mutagen . NEU is found to induce in bacterial DNA only base pair substitutions; NMU and NDMU - deletions and base pair substitutions . An original model of deletion mechanism with Goldwait endonuclease II participation is proposed.

Dev Biol Stand, 1976, 33, 85 - 8
Vaccination against typhoid fever with a live oral vaccine; Germanier R; A Salmonella typhi gal E mutant, designated Ty 21a, has been developed on the basis of virulence and protection studies with similar Salmonella typhimurium mutants in mice . Gal E mutants are characterized by a block in the enzyme UDP-4-galactose-epimerase . They owe their outstanding immunizing capacity when used in live oral vaccine to the fact that when galactose is supplied exogenously, as occurs in vivo, wild-type cell wall structures are synthesized . On the other hand, avirulence of these mutants is based upon the fact that when galactose is taken up it is partly accumulated as galactose-1-phosphate and UDP-galactose, which induces lysis of the bacteria . Strain S . typhi Ty 21a does not revert to wild type in vivo and in vitro . Its safety for man has been demonstrated in studies involving 137 adults and 370 children . S . typhi Ty 21a also has been shown to protect against challenge with virulent S . typhi in human volunteers.

Dev Biol Stand, 1976, 33, 118 - 23
Compared efficiency of a killed vaccine of Salmonella typhimurium, a live vaccine and an antigenic fraction in oral immunization of mice; Fontanges R et al.; In an attempt to determine the best method of immunizing mice by oral route against Salmonella typhimurium, the animals were vaccinated by means of a killed-pathogenic strain, an avirulent mutant of the same bacteria, and a protective antigen removed from the supernatant culture of this mutant . After changing doses of vaccines and the interval between vaccination and challenge, the results obtained show the superiority of the live vaccine and protective antigen with regard to the killed one . Under our experimental conditions enteral vaccination appears to be more effective than the parenteral one.

J Supramol Struct, 1976, 4(3), 329 - 42
Studies of bacterial chemotaxis in defined concentration gradients . A model for chemotaxis toward L-serine; Dahlquist FW et al.; The details of the chemotactic response of Salmonella typhimurium to gradients of L-serine have been examined in some detail . Two relatively macroscopic techniques have been employed to measure the bacterial response . These include measurements of the average velocity as the bacterial population moves toward attractants, and measurement of the upward-to-downward flux ratio, R, in the stable preformed attractant gradients . The dependence of the average velocity on gradient appears to be hyperbolic in nature, while the flux ratio depends linearly on the gradient . These data suggest a microscopic model for the dependence of bacterial behavior on the serine gradient . The model involves a linear dependence of the mean lifetime of a bacterial trajectory on the gradient for those bacteria moving toward higher attractant concentration . Those moving toward low concentrations of attractant do not change the mean duration of their trajectories, or the speed at which a given bacterium swims through the solution . This model generates the observed dependences of the average velocity and flux ratio on gradient . Interpretation of the experimental data suggests that a gradient which increases serine concentration by a factor of 2 in 10 mm is sufficient to double the average duration of a trajectory for a bacterium moving directly up the gradient . The concentration dependence of the chemotactic response to serine is more complicated . It suggests that more than one receptor of serine may be involved in determining chemotactic behavior to this attractant.

J Supramol Struct, 1976, 4(3), 305 - 17
Chemotaxis in bacteria; Adler J; Bacterial chemotaxis, the movement of motile bacteria toward or away from chemicals, was discovered nearly a century ago by Engelmann (1) and Pfeffer (2,3) . The subject was actively studied for about 50 years, but then there were very few reports until quite recently . For reviews of the literature up to about 1960, see Berg (4), Weibull (5), and Ziegler (6) . The present review will restrict itself to the recent work on chemotaxis in Escherichia coli and Salmonella typhimurium . Some of this is also covered in Berg's review (4), and a review by Parkinson (7) should be consulted for a more complete treatment of the genetic aspects.

Mutat Res, 1976 Jan, 40(1), 9 - 14
Mutagenicities of nitrofuran derivatives on a bacterial tester strain with an R factor plasmid; Yahagi T et al.; Many nitrofuran derivatives are known to be mutagenic on Escherichia coli WP2 but not on Salmonella typhimurium TA1535, TA1536, TA1537 or TA1538 . Ames and coworkers recently obtained a new tester strain of S . typhimurium, TA100, by putting an R factor plasmid, pKM101, into TA1535 . We found that all mutagenic nitrofuran derivatives previously found to be mutagenic on E . coli WP2 were mutagenic on this new strain (TA100).

Mutat Res, 1976 Jan, 34(1), 35 - 42
Spontaneous and induced mutability or frameshift strains of Salmonella typhimurium carrying uvrB and polA mutations; Imray FP et al.; Three strains of Salmonella typhimurium carrying frameshift mutations affectin g the histidine genes (hisC3076, hisD3052 and hisC207) showed increased sensitivity to mutagenesis by ICR-191 (as judged by measuring back mutation to prototrophy), if they were made deficient in excision repair by deleting the uvrB gene . One frameshift strain, hisC3076, also showed increased sensitivity to mutagenesis by ICR-191 when it carried either of two different polA alleles, whereas the hisD3052 and hisC207 frameshifts reduced sensitivity to mutagenesis in the presence of these alleles . Studies of spontaneous back mutation to prototrophy revealed significant mutator effects of the polA1 mutation on reversion of the hisD3052 frameshift and of the polA3 mutation on reversion of the hisC3076 frameshift . Other smaller mutator effects of the polA alleles on complex interactions between different polA alleles and different frameshift mutations, it is tentatively suggested that deletion frameshifts may arise mainly during DNA replication, while addition frameshifts may arise mainly during post-replication repair.

Genetika, 1976, 12(5), 119 - 25
{Effect of mutagenic metabolic activation of N-nitrosomorpholine on microorganisms}; Fonshtein LM et al.; Almost similar sensitivity is demonstrated of different methods of studying mutagenic metabolic activation of N-nitrosomorpholine (NM) in Salmonella typhimurium TA 1950 (host-mediated assay and the system of metabolic activation with rat liver homogenate) . The role of correlation of certain ingredients of NM metabolic activation system with homogenates (homogenate and cofactor NADPH concentrations) is studied . The fact of influence of microsome protein activator (phenobarbital) on the NM mutagen activation effect is established.

Acta Biochim Pol, 1976, 23(1), 57 - 68
The synthesis and properties of N6-substituted 2-amino-purine derivatives; Janion C; 1 . The synthesis, ultraviolet absorption spectra, and behaviour in alkali of N6-methoxy-, N6-methyl, hydroxy-, and N6-hydroxy-2-aminopurines have been described 2 . N6-Methoxy-2-aminopurine riboside 5'-pyrophosphate has been prepared and used for polymerization with polynucleotide phosphorylase . 3 . The copolymer containing N6-methoxy-2-aminopurine riboside and adenosine residues has been obtained; attempts to synthesize the homopolymer have not been successful . 4 . All the purine analogues synthesized have been tested and shown to act mutagenically on Salmonella typhimurium TA1530.

C R Acad Sci Hebd Seances Acad Sci D, 1975 Dec 22, 281(24), 2037 - 40
{The effect of an inflammatory reaction on the resistance of mice to infection by Listeria monocytogenes and Salmonella typhimurium}; Fauve RM et al.; Following subcutaneous acute inflammatory reactions in mice, the blood clearance of virulent Salmonella typhimurium was enhanced and the multiplication of Listeria monocytogenes in spleen and liver was decreased.

J Am Vet Med Assoc, 1975 Dec 15, 167(12), 1089 - 90
Salmonellosis in a human infant, a cat, and two parakeets in the same household; Madewell BR et al.; Salmonellosis occurred in a human infant, cat, and 2 pet parakeets in the same household . Salmonella typhimurium var copenhagen was isolated from all 4 subjects; however, its original source was never determined . The parakeets subsequently died, and necropsy revealed enteritis, foci of hepatic necrosis, and leptomeningitis.

J Bacteriol, 1975 Dec, 124(3), 1273 - 81
Fine-structure genetic map of the cysB locus in Salmonella typhimurium; Cheney RW Jr et al.; A genetic map of the cysB region of the Salmonella typhimurium chromosome was constructed using bacteriophage P22-mediated transduction . Strains bearing delta (supX cysB) mutations were employed to divide this regulatory locus into 12 segments containing a total of 39 single-site mutations . Twenty-five of these single-site mutations were further ordered by reciprocal three-point crosses . The results do not support the concept of multiple cistrons at cysB and suggest that the abortive transductants previously observed in crosses between certain cysB mutants were due to intracistronic complementation . The prototrophic cys-1352 mutation, which causes the constitutive expression of the cysteine biosynthetic enzymes, was found to lie within the cysB region itself . It is bracketed by mutations, which lead to an inability to derepress for these enzymes and result in auxotrophy for cysteine.

Proc Natl Acad Sci U S A, 1975 Dec, 72(12), 5021 - 5
Regulation of histidine operon does not require hisG enzyme; Scott JF et al.; Mutations are described which delete all or part of the first structural gene (hisG) of the histidine operon of Salmonella typhimurium . Physiological regulation of histidine enzymes occurs normally in strains carrying any deletion that has both endpoints within the hisG gene . Constitutive high operon expression is observed in strains carrying any hisG deletion and an unlinked regulatory mutation, hisT1504 . These results strongly indicate that the hisG protein is not an essential component of the mechanism for regulating expression of the histidine operon.

Mutat Res, 1975 Dec, 30(3), 305 - 15
The relationship of 2-acetamidofluorene mutagenicity in plate tests with its in vivo liver cell component distribution and its carcinogenic potential; McGregor D; Using a plating technique, the mutagenic potentials of 2-acetamidofluorene (AAF) and N-hydroxy-AAF were examined after metabolic activation by liver preparations from different animals . Animals used were: male and female rats; male rats treated with 3-methylcholanthrene (MC); male rats treated with AAF; hamsters; guinea pigs; cotton rats and baboons . Irrespective of the animal susceptibility to AAF carcinogenesis, mutation frequency was always increased in the Salmonella typhimurium TA 1538 tester strain . Indeed, the greater response was found in the presence of liver from cotton rats, a species which is resistant to AAF-induced carcinogenesis . Carcinogen binding, with labelled molecules, was also studied in liver cell constituents of rats, guinea pigs and cotton rats . A much better correlation was found between carcinogenicity and carcinogen binding, at least in those species studied, than between carcogenicity and plate test mutagenicity . The difficulty which this new information poses for the interpretation of plate tests is discussed.

J Infect Dis, 1975 Dec, 132(6), 617 - 22
Antimicrobial resistance and R-factor transfer among isolates of Salmonella in the northeastern United States: a comparison of human and animal isolates; Neu HC et al.; The antimicrobial susceptibility of 718 isolates of Salmonella from humans and of 688 isolates from animals was examined . Of the 46 different serotypes among the isolates from humans, Salmonella typhimurium accounted for 34% . Thirty percent of isolates were resistant to one or more antibiotic(s) . Resistance to streptomycin was most common; resistance to tetracycline was next most common . Over 50% of isolates of S . typhimurium and Salmonella newport were resistant to four antibiotics . Resistance to tetracycline, kanamycin, and ampicillin has increased steadily during the past decade . Most strains possessed R-factors, and resistance to ampicillin, streptomycin, sulfisoxazole, tetracycline, chloramphenicol, and kanamycin (but not that to cephalothin) was transferable . Among the salmonellae commonly isolated from humans, only Salmonella enteritidis showed limited resistance to antibiotics (5.8%) . Antibiotic resistance of isolates of S . typhimurium, Salmonella saint-paul, and Salmonella heidelberg from animals was similar to the resistance of isolates from humans . Resistance to kanamycin increased markedly over the level noted in previous studies . R-factor prevalence was high . Antibiograms of the isolates from animals and humans were similar, although some patterns were seen only in isolates from one source . Ampicillin resistance was more common in human isolates, and resistance to tetracycline, sulfonamide, and streptomycin was more common in animal isolates . Salmonellae of serotypes other than S . typhimurium that came from humans were less resistant to all antibiotics than were isolates from animals.

J Bacteriol, 1975 Dec, 124(3), 1630 - 4
Transfectability of rough strains of Salmonella typhimurium; Bursztyn H et al.; Cells of rough (but not smooth) strains of Salmonella typhimurium become competent for transfection by phage P22 deoxyribonucleic acid after treatment with 0.1 M CaCl2 . The yield of infectious centers is about 10(-8) per genome equivalent of deoxyribonucleic acid . However, different sorts of rough strains vary in their ability to become competent in a fashion that can be correlated with the level of the genetic block in cell wall lipopolysaccharide synthesis . The most amenable strains are blocked by defects in the addition of galactose units I and II of the lipopolysaccharide by the inability to synthesize uridine 5'-diphosphate-galactose (galE point mutants and gal deletion mutants) . Strains blocked only in the addition of galactose I, glucose I, or heptose II have low levels of transfectability, whereas strains with either more complete or more deficient lipopolysaccharide core are not competent for transfection . When normal lipopolysaccharide synthesis is restored either genetically or by furnishing exogenous galactose (galE point mutants that can still use it), the cells are not longer competent for transfection.

J Bacteriol, 1975 Dec, 124(3), 1351 - 8
Genes affecting coliphage BF23 and E colicin sensitivity in Salmonella typhimurium; Guterman SK et al.; Rough strains of Salmonella typhimurium were sensitive to coliphage BF23 . Spontaneous mutants resistant to BF23 (bfe) were isolated, and the trait was mapped using phage P1 . The bfe gene in S . typhimurium was located between argF (66% co-transducible) and rif (61% co-transducible) . The BF23-sensitive S . typhimurium strains were not sensitive to the E colicins . Cells of these rough strains absorbed colicin, as measured by loss of E2 or E3 killing units from colicin solutions and by specific adsorption of 125I-colicin E2 to bfe+ cells . Sensitivity to colicins E1, E2, and E3 was observed in a S . typhimurium strain carrying the F'8 gal+ episome . This episome complemented the tolB mutation of Escherichia coli . We conclude that the bfe+ protein satisfies requirements for adsorption of both phage BF23 and the E colicins . In addition, expression of a gene from E . coli, possibly tolB, is necessary for efficient E colicin killing of S . typhimurium.

J Bacteriol, 1975 Dec, 124(3), 1227 - 35
trans-Recessive mutation in the first structural gene of the histidine operon that results in constitutive expression of the operon; Meyers M et al.; The first enzyme for histidine biosynthesis, encoded in the hisG gene, is involved in regulation of expression of the histidine operon in Salmonella typhimurium . The studies reported here concern the question of how expression of the histidine operon is affected by a mutation in the hisG gene that alters the allosteric site of the first enzyme for histidine biosynthesis, rendering the enzyme completely resistant to inhibition by histidine . The intracellular concentrations of the enzymes encoded in the histidine operon in a strain carrying such a mutation on an episome and missing the chromosomal hisG gene are three- to fourfold higher than in a strain carrying a wild-type hisG gene on the episome . The histidine operon on such a strain fails to derepress in response to histidine limitation and fails to repress in response to excess histidine . Furthermore, utilizing other merodiploid strains, we demonstrate that the wild-type hisG gene is trans dominant to the mutant allele with respect to this regulatory phenomenon . Examination of the regulation of the histidine operon in strains carrying the feedback-resistant mutation in an episome and hisT and hisW mutations in the chromosome showed that the hisG regulatory mutation is epistatic to the hisT and hisW mutations . These data provide additional evidence that the first enzyme for histidine biosynthesis is involved in autogenous regulation of expression of the histidine operon.

Cancer Res, 1975 Dec, 35(12), 3811 - 23
The reactivity and carcinogenicity of aflatoxin B1-2,3-dichloride, a model for the putative 2,3-oxide metabolite of aflatoxin B1; Swenson DH et al.; Aflatoxin B1-2,3-dichloride (AFB1-Cl2) was synthesized as a model for the probable ultimate carcinogen, aflatoxin B1-2,3-oxide . As expected for aflatoxin B1-2,3-oxide, AFB1-Cl2 has an electrophilic carbon 2; it decomposed in water (half-life of 0.5 min in 10% dimethyl sulfoxide, pH 7.4) with the formation of 3-chloro-2,3-dihydro-2-hydroxyaflatoxin B1 and 2,3-dihydro-2,3-dihydroxyaflatoxin B1 . AFB1-Cl2 formed covalent adducts with DNA and RNA with retention of one-half of the chlorine; the major products apparently contained glycosidic bonds between carbon 2 of the aflatoxin residues and nitrogen or oxygen atoms in the nucleic acids . Polyguanylic acid was the most reactive homopolymer toward AFB1-Cl2 . AFB1-Cl2 was less reactive toward mononucleotides than toward polynucleotides . The major adducts formed on incubation of AFB1-Cl2 with protein contained little chlorine and could have resulted from alkylation of primary amino groups or from reactions with the hydrolysis products . Similarly, incubation of AFB1-Cl2 with amino acids apparently resulted in Schiff base formation between primary amino groups and the dialdehyde rearrangement forms of the hydrolysis products of AFB1-Cl2 . AFB1-Cl2 was much more active than aflatoxin B1 in inducing sarcomas at the s.c . injection site in rats, in the initiation of papillomas on the skin of mice, and in the induction of lung tumors in mice . AFB1-Cl2 was also highly mutagenic for Salmonella typhimurium TA 98 and TA 100 . Aflatoxin B1 and its 2,3,-dihydro- (aflatoxin B2), 2,3-dihydro-2-hydroxy- (aflatoxin B2a), 2,3-dihydro-2,3-dihydroxy-, and 3-chloro-2,3-dihydro-2-hydroxy- derivatives were inactive in the mutagenicity tests; and the latter four compounds were also inactive as initiators of papillomas of the skin in mice . The structures of the macromolecular adducts of AFB1-Cl2 formed in vitro, the carcinogenicity of this electrophile, and the lack of carcinogenicity of its hydrolysis products indicate that alkylation of nucleic acids is a critical reaction in tumor induction with this carcinogen and aflatoxin B1.

Cancer Res, 1975 Dec, 35(12), 3611 - 7
Mutagenicity of nitrofurans, nitrothiophenes, nitropyrroles, nitroimidazole, aminothiophenes, and aminothiazoles in Salmonella typhimurium; Wang CY et al.; Thirty-two heterocyclic compounds, including 24 nitroheterocycles, 7 aminoheterocycles and derivatives, and 1 thiophene lacking a nitro group, were tested for mutagenic activity in Salmonella typhimurium TA 98 and TA 100 . All the nitroheterocycles (11 new), including nitrofurans, nitrothiophenes, nitropyrroles, and 1 nitroimidazole, were mutagenic in TA 100; 13 were also mutagenic in TA 98 . 5-Nitro-2-furoic acid, a noncarcinogen, was mutagenic in TA 100 . Seven carcinogenic nitroheterocycles were mutagenic in both strains . Seven aminoheterocycles (4 new), aminothiophenes and aminothiazole derivatives, and 1 thiophene without a nitro group were not mutagenic . Both TA 98 and TA 100 were uvrB and lacked the ability of excision repair of DNA . Among the 24 mutagenic nitroheterocycles, only 13 compounds exhibited bacterial killing effects, suggesting that more than 1 mechanism may be involved in the interaction of nitroheterocycles with bacterial DNA.

Aust J Biol Sci, 1975 Dec, 28(5-6), 559 - 65
Mutants of Salmonella typhimurium deficient in DNA polymerase I: further characterization and genetic analysis; MacPhee DG et al.; Tests with a plasmid-borne ochre suppressor (sup-812) and a chromosomal amber suppressor (supD501) revealed that one of three mutants of S . typhimurium deficient in DNA polymerase I was an amber mutant . Assays performed on crude extracts established that derivatives of this mutant (designated polA3) carrying ochre and amber suppressors had about 13 to 20% respectively of the enzyme activity found in the wild-type parent . The unsuppressed mutant showed less than 1% of the wild-type level of activity . Other properties of the polA3 mutant that were also partially or in some cases completely reversed by the sup-812 and supD501 suppressors included: u.v . sensitivity, methyl methanesulphonate (MMS) sensitivity, reduced ability to effect host-cell reactivation of u.v.-irradiated or MMS-treated bacteriophages, inability to maintain the (Col El) plasmid, and reduced ability to plate the phage mutant P22 c2 hpi-308 . Mapping by P1-mediated transduction showed that all three polA mutations lie between metE and rha on the S . typhimurium chromosome, and that the polA mutation is cotransduced with metE at a frequency of 20% and with rha at a frequency of 8%.

Mol Biol Rep, 1975 Dec, 2(4), 295 - 301
Pyrimidine nucleoside analogues as inducers of pyrimidine nucleoside catabolizing enzymes in Salmonella typhimurium; Krajewska E et al.; Various structural analogues of cytosine and uracil nucleosides were tested as potential inducers of the nucleoside catabolizing (cyt) enzymes in Salmonella typhimurium . Some analogues, e.g . 5'-O-alkyl cytidines and uridines, resistant to catabolic enzymes, were as effective as the natural inducers cytidine and uridine; but etherification of one of the cis 2' or 3'hydroxyls fully abolished activity, pointing to a requirement of an intact ribose cis-glycol system for activity . A uridine analogue in the syn conformation, 6-methyluridine, a good substrate for uridine phosphorylase, was inactive as an inducer . The behavior of various other analogues, in relation to their structure, conformation and substrate properties, indicated the absence of any correlation between inducing activity and substrate susceptibility . The overall findings are consistent with conclusions derived from genetic experiments . The active analogues apparently act via similar pathways, and probably affect the same regulatory mechanism(s) as the natural inducers.

Gastroenterology, 1975 Dec, 69(6), 1238 - 45
Pathogenesis of Salmonella-mediated intestinal fluid secretion . Activation of adenylate cyclase and inhibition by indomethacin; Giannella RA et al.; Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms . To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S . typhimurium . Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion . Cholera toxin-stimulated loops were also studied . When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities . SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities . Indomethacin pretreatment of cyclase activation . In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase . These results suggest that: (1) S . typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion . The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin . This might be explained by the participation of prostaglandins in the salmonella activation process.

J Bacteriol, 1975 Dec, 124(3), 1312 - 20
3-Deoxy-D-arabino-heptulosonic acid 7-phosphate synthase mutants of Salmonella typhimurium; DeLeo AB et al.; The first committed step of aromatic amino acid biosynthesis in Salmonella typhimurium was shown to be catalyzed by three isoenzymes of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) synthase . Mutations in each of the genes specifying the isoenzymes were isolated and mapped . aroG, the structural gene for the phenylalanine-inhibitable isoenzyme, was linked to gal, and aroH, the structural gene for the tryptophan-inhibitable isoenzyme, was linked to aroE . aroF, the structural gene for the tyrosine-inhibitable isoenzyme, was linked to pheA and tyrA, which specify the phenylalanine- and tyrosine-specific branch-point enzymes, respectively . The phenylalanine-inhibitable isoenzyme was the predominant DAHP synthase in wild-type cells, and only the tryosine-inhibitable isoenzyme was completely repressed, as well as inhibited, by low levels of its allosteric effector . The DAHP synthase isoenzymes were separated by chromatography on diethylaminoethyl-cellulose with a phosphate gradient which contained enolpyruvate phosphate to protect the otherwise unstable phenylalanine-inhibitable isoenzyme . No cross-inhibition of either the tyrosine- or phenylalanine-inhibitable isoenzyme was observed at inhibitor concentrations up to 1 mM . The tryptophan-inhibitable isoenzyme was partially purified from extracts of a strain lacking the other two isoenzymes and shown to be inhibited about 30% by 1 mM tryptophan . A preliminary study of interference by tryptophan in the periodate-thiobarbiturate assay for DAHP suggested a combined effect of tryptophan and erythrose 4-phosphate, or an aldehydic compound resulting from degradation of erythrose 4-phosphate by periodate.

J Bacteriol, 1975 Dec, 124(3), 1269 - 72
Regulation of the hut operons of Salmonella typhimurium and Klebsiella aerogenes by the heterologous hut repressors; Gerson SL et al.; In merodiploid strains of Klebsiella aerogenes with chromosomal hut genes of K . aerogenes and episomal hut genes of Salmonella typhimurium, the repressor of either species can regulate the hut operons of the other species . The repression exerted by the homologous repressor on the left-hand hut operon is, in both organisms, stronger than that exerted by the heterologous repressor.

J Bacteriol, 1975 Dec, 124(3), 1263 - 8
Expression of the hut operons of Salmonella typhimurium in Klebsiella aerogenes and in Escherichia coli; Parada JL et al.; The normal hut (histidine utilization) operons, as well as those with mutations affecting the regulation of their expression, of Salmonella typhimurium were introduced on an F' episome into cells of S . typhimurium and Klebsiella aerogenes whose chromosomal hut genes had been deleted and into cells of Escherichia coli, whose chromosome does not carry hut genes . The episomal hut operons respond in a manner very similar to induction and catabolite repression in all three organisms . The small differences found reflect both different abilities to take up inducers from the medium and different degrees of catabolite repression exerted by glucose.

Mol Gen Genet, 1975 Nov 24, 141(2), 173 - 9
Genetic analysis of mutants of Escherichia coli K12 and Salmonella typhimurium LT2 deficient in hydrogenase activity; Pascal MC et al.; A genetic study of mutants deficient in hydrogenase activity was performed . In E . coli, the affected gene (hyd) is located at 51 min, between cys C and nal B; in S . typhimurium, it probably lies in the homologous region of the chromosome.

Biochemistry, 1975 Nov 18, 14(23), 5061 - 7
Studies on the Methyl Green-DNA complex and its dissociation by drugs; Krey AK et al.; Spectrophotometric results indicated that Methyl Green bound stably to native calf thymus DNA and to poly{d(A-T)} but to a lesser extent to phiX 174 DNA, tRNAs, and poly(dG-dC), a copolymer that exists preferentially in the A conformation . Exposing the Methyl Green-DNA complex to graded concentrations of ethyl alcohol liberated part of the dye slowly by a zero-order reaction; higher alcohol concentrations which cause the B leads to A transition of DNA released the bulk of Methyl Green . The viscosity of the Methyl Green-DNA complex was significantly lower than that of the uncomplexed DNA . The dye was progressively liberated from DNA by 1.5 x 10(-1) M NaCl and by much lower concentrations of Mg2+; in its stoichiometric complex with DNA, it increased Tm by approximately 12 degrees C . A series of DNA-complexing drugs displaced Methyl Green from DNA at exponential rates and to end points which were correlated . End points of displacement correlated with the abilities of drugs to unwind supercoiled DNA, to labilize ribosomes to heat, and to eliminate a kanamycin resistance determinant from an R factor carried by Salmonella typhimurium . Additional correlations between Methyl Green displacement and biochemical-biological activities of displacing drugs are cited . In conjunction with these findings, our results suggest that Methyl Green displacement analysis is a useful biochemical screen for the detection or development of biologically active compounds which bind to DNA.

Int J Cancer, 1975 Nov 15, 16(5), 787 - 97
Epoxides metabolically produced from some known carcinogens and from some clinically used drugs . I . Differences in mutagenicity; Glatt HR et al.; The epoxide metabolites of two clinically used drugs and an experimental psychotropic agent, carbamazepine 10,11-oxide, cyproheptadine 10,11-oxide and cyclobenzaprine 10,11-oxide, were fully devoid of any mutagenic activity under conditions where K-region-epoxide metabolites of some known carcinogens, such as benzo(a)pyrene, proved to be potent frameshift mutational agents for Salmonella typhimurium TA 1537 and TA 1538 . All epoxides tested were non-mutagenic for TA 1535, designed to detect substitution mutations . The 10,11-epoxides of the three drugs, carbamazepine, cyproheptadine and cyclobenzaprine, were not cytotoxic to any of the bacterial tester strains used, precluding that mutagenicity might have been overshadowed by cytotoxicity . When the mutagen, precursor, benzo(a)pyrene, was incubated together with TA 1537 and a mammalian microsomal preparation in the presence of a system generating the co-factor necessary for mono-oxygenase activity, activation to mutagenic species was observed which was dramatically increased in the presence of a potent epoxide hydratase inhibitor, 1,1,1-trichloropropene 2,3-oxide, suggesting epoxide(s) as the (or one of the) mutagenically active species metabolically produced in situ . None of these effects was observed with the three medical drugs . Moreover, the observation that the alkene oxide 4-phenylstyrene 7,8-oxide is mutagenic to the two strains TA 1537 and TA 1538 but the K-region arene oxide derived from 7,12-dimethylbenz(a)anthracene is inactive for the latter strain indicates that epoxidation of an aromatic double bond of a polycyclic hydrocarbon is neither a necessary nor a satisfying condition for frameshift mutagenesis to occur.

J Toxicol Environ Health, 1975 Nov, 1(2), 211 - 7
A comparative study on the genetic effects of hycanthone and oxamniquine; Ray VA et al.; Oxamniquine (UK-4271; 6-hydroxymethyl-2-isopropylaminomethyl-7-nitro-1,2,3,4-tetrahydroquinoline) is a new schistosomicidal agent currently undergoing clinical investigation in South America . Essentially a complete cure rate against Brazilian Schistosoma mansoni has been seen in adults with a single im dose of 7.5 mg/kg or a single oral dose of 15 mg/kg . These regimens were tolerated without significant toxicity . To assess its mutagenic potential, oxamniquine was examined in a battery of genetic tests designed to detect mutations at the gene and chromosome levels . For comparative purposes, hycanthone, a schistosomicide with extensively studied mutagenic properties, was evaluated in a similar series of tests . Point mutations were measured in a series of histidineless auxotrophs of Salmonella typhimurium in direct plate and host-mediated assays . Gross chromosomal aberrations were assessed in human leucocyte cultures and in bone marrow preparations from drug-treated mice . Effects on germ cells were tested in the dominant-lethal assay . Hycanthone showed significant mutagenic activity in the direct bacterial tests and the in vivo and in vitro cytogenetic assays . No response was detected in the host-mediated or dominant-lethal assays . On the other hand, oxamniquine produced no drug-related mutagenic effects in the cytogenetic, host-mediated, or dominant-lethal tests at doses up to 150 mg/kg administered parenterally . Oxamniquine produced a weak response in the frameshift mutant, TA1538, of Salmonella typhimurium in direct plate tests with and without liver microsomal enzymes . However, this response was achieved only by using a concentration of compound which was several orders of magnitude higher than that required to produce a similar response to hycanthone.

Biochim Biophys Acta, 1975 Nov 4, 407(4), 459 - 68
Substrate specificity of Salmonella typhimurium RNAase III and the nature of products formed; Suryanarayana T et al.; RNAase III, an endonuclease specific for double-stranded substrates, has been obtained in a highly purified form from extracts of Salmonella typhimurium . Poly (I-C) and a mixture of poly(A) and poly(U) (1 : 1), the latter in presence of 5 mM Mg2+, act as excellent substrates . Poly(I-C) is only partially hydrolysed by RNAase III and the product or products are acted upon by both RNAase I and RNAase II indicating that the products may be oligonucleotides . This conclusion is supported by two-dimensional chromatography on DEAE paper.

Proc Natl Acad Sci U S A, 1975 Nov, 72(11), 4607 - 11
Association of salmonella mutants with germfree rats: site specific model to detect carcinogens as mutagens; Wheeler LA et al.; An association of the histidine auxotroph of Salmonella typhimurium (strain TA1538) within the gastrointestinal tract of otherwise germfree Sprague-Dawley rats is maintained during periods of observation lasting as long as 7 months . The bacteria are found at levels exceeding 10(7) per g in the forestomach and at levels greater than 10(8) per g in the lower bowel and in the feces . Only approximately 10(4) bacteria per g are found in the posterior stomach and in the upper small intestine . The association of the salmonella mutants is maintained when the bacterial association is increased by the addition of other bacteria characteristic of the gastrointestinal flora . Carcinogenic amines, which cause strain TA1538 to revert to histidine independence in Ames' in vitro assays, increase the number of revertants in the feces when fed to the salmonella-associated rats . In contrast, the number of revertants in the feces does not increase when the rats are fed structurally related compounds which are not mutagenic to the bacteria in vitro and for which no evidence of carcinogenicity exists . Sacrifice of rats after feeding the carcinogen 2-nitrofluorene indicates that the number of revertants is increased in the cecum and colon as well as in the feces . The apparent proximity of the bacterial mutagenic response to the location of the tumor response in the colon suggests that the rat associated with the histidine auxotroph may provide a useful model for further investigation of the possible association between bacterial mutagenesis and carcinogenesis within the gastrointestinal tract . In addition, with this model it may be possible to evaluate selectively the effects of various constituents of the flora on the activation of compounds provoking the revertant response.

Proc Natl Acad Sci U S A, 1975 Nov, 72(11), 4389 - 93
Guanosine 5'-diphosphate 3'-diphosphate (ppGpp): positive effector for histidine operon transcription and general signal for amino-acid deficiency; Stephens JC et al.; Maximal expression of the histidine operon of Salmonella typhimurium in a coupled in vitro transcription-translation system is strongly dependent upon addition of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) . This requirement for ppGpp is exerted at the level of transcription through a mechanism distinct from the his-operon-specific regulatory mechanism . In vivo derepression of the his operon is markedly defective when histidine starvation is imposed on a relA mutant--unable to rapidly increase synthesis of ppGpp--growing in amino-acid-rich medium . Increased sensitivity of relA mutants to growth inhibition by a number of amino-acid analogs suggests that ppGpp is generally important in adjusting expression of amino-acid-producing systems . Analysis of these findings leads us to propose that ppGpp is a positive effector in a system that enables the cell to balance endogenous amino-acid production with environmental conditions of amino-acid availability, and to compensate efficiently for transient changes in these conditions . We propose a unifying theory of the role of ppGpp as the general signal molecule (alarmone) in a "super-control" which senses an amino-acid deficiency and redirects the cell's economy in response.

Infect Immun, 1975 Nov, 12(5), 993 - 8
Effect of lipopolysaccharide and lipid A on mouse liver pyruvate kinase activity; Smith SM et al.; Several investigators have reported lipid A as the biologically active unit in the lipopolysaccharide (LPS) molecule . To determine if lipid A was responsible for the reported increases in pyruvate kinase, mice were injected with endotoxin from Salmonella typhimurium SR-11, the Re mutant of Salmonella minnesota R 595, and lipid A-bovine serum albumin conjugate . The livers were homogenized and the activity of pyruvate kinase was measured . Similar increases in enzyme were obtained with all three preparations . These data imply that the lipid portion of the LPS molecule was responsible for alterations in host enzyme activity . To further determine if the lipid portion was the active unit, a lipid-degraded endotoxin (endotoxoid) prepared by potassium methylate treatment was inoculated into mice . An initial increase in liver pyruvate kinase activity was observed with all preparations . The marked increase observed at 16 h with the native product and lipid A conjugate was not obtained with the endotoxoid . These experiments extend and confirm previous observations that lipid A is responsible for the effects associated with LPS . Animals tolerant to endotoxin from S . typhimurium SR-11 were challenged with endotoxin from the Re mutant . A significant increase in pyruvate kinase activity was not obtained, suggesting that anti-O antibodies are not important in the development of tolerance.

Chem Biol Interact, 1975 Nov, 11(5), 469 - 72
Mutagenic activity of platinum and ruthenium complexes; Monti-Bragadin C et al.; cis-Dichlorodiammineplatinum(II) {cis-PtCl2(NH3)2} and dichlorotetrakis (dis-methylsulfoxide) ruthenium(II) {RuCl2(DMSO)4} have been tested as mutagens for strains of Salmonella typhimurium carrying the hisG46 missense mutation . Their activity, which has been compared with the activity of mitomycin C, depends on the presence in the test bacteria of the pKM101 plasmid and is affected in various ways by the function of the excision repair system . More precisely, mitomycin C is mutagenic only for strains with an intact uvr system . cis-PtCl2(NH3)2 and RuCl2(DMSO)4 are mutagens both for uvrB and uvr+ strains, but cis-PtCl2(NH3)2 is more active on the latter, while the converse is true for RuCl2(DMSO)4 . It seems, therefore, that each drug interacts with DNA by a different mechanism.

J Bacteriol, 1975 Nov, 124(2), 942 - 58
Outer membrane of Salmonella typhimurium: chemical analysis and freeze-fracture studies with lipopolysaccharide mutants; Smit J et al.; The outer membrane layer of the cell wall was isolated from wild-type Salmonella typhimurium LT2 as well as from its mutants producing lipopolysaccharides with shorter saccharide chains . Chemical analysis of these preparations indicated the following . (i) The number of lipopolysaccharide molecules per unit area was constant, regardless of the length of the saccharide side chain in lipopolysaccharide . (ii) In contrast, in "deep rough" (Rd or Re) mutants producing the lipopolysaccharides with very short saccharide chains, the amount of outer membrane protein per unit surface area decreased to about 60% of the value in the wild type . (iii) In the wild type, the amount of phospholipids is slightly less than what is needed to cover one side of the membrane as a monolayer . In comparison with the wild type, the outer membrane of Rd and Re mutants contains about 70% more phospholipids, which therefore must be distributed in both the outer and inner leaflets of the membrane . Freeze-fracture studies showed that the outer membrane of Re mutants were easily fractured, but fracture became increasingly difficult in strains producing lipopolysaccharides with longer side chains . The convex fracture face was always nearly smooth, but the concave fracture face or the outer half of the membrane was densely covered with particles 8 to 10 nm in diameter . The density of particles was decreased in Re mutants to the same extent as the reduction in proteins, suggesting the largely proteinaceous nature of particles . A model for the supramolecular structure of the outer membrane is presented on the basis of these and other results.

J Bacteriol, 1975 Nov, 124(2), 930 - 41
Comparison of the cell envelope structure of a lipopolysaccharide-defective (heptose-deficient) strain and a smooth strain of Salmonella typhimurium; Irvin RT et al.; The cell envelope structure of Salmonella typhimurium LT2, which has a heptose-deficient lipopolysaccharide (LPS), is significantly different from that of an isogenic strain with a normal LPS . The rough strain, when examined by freeze-etching, lacks most surface structures that are routinely present in the smooth strain (surface particles and flagella) and has few transmemberane studs in the cytoplasmic membrane (those present are generally found in aggregates), and the outer membrane cleavage is substantially stronger than that of the smooth strain . These envelope differences were independent of both growth temperature and culture age . Examination of ultrathin sections indicated that the rough strain has an outer membrane which forms a much more defined double-track artifact than the smooth strain . The addition of MgCl2 to the growth medium of the rough strain decreased the extent of outer membrane cleavage, and flagella became evident in freeze-etched preparations . The presence of supplemental MgCl2 in the growth medium, which resulted in these morphological changes in the rough strain, also produced growth at a previously restrictive temperature and a decrease in the leakage of periplasmic enzymes . The smooth strain was unaltered morphologically or physiologically by MgCl2 under identical conditions . It is suggested that the outer membrane of the rough strain is more planar.

J Bacteriol, 1975 Nov, 124(2), 764 - 74
Pyrimidine biosynthetic enzymes of Salmonella typhimurium, repressed specifically by growth in the presence of cytidine; Kelln RA et al.; The repressive effects of exogenous cytidine on growing cells was examined in a specially constructed strain in which the pool sizes of endogenous uridine 5'-diphosphate and uridine 5'-triphosphate cannot be varied by the addition of uracil and/or uridine to the medium . Five enzymes of the pyrimidine biosynthetic pathway and one enzyme of the arginine biosynthetic pathway were assayed from cells grown under a variety of conditions . Cytidine repressed the synthesis of dihydroorotase (encoded by pyrC), dihydroorotate dehydrogenase (encoded by pyrD), and ornithine transcarbamylase (encoded by argI) . Moreover, aspartate transcarbamylase (encoded by pyrB) became further derepressed upon cytidine addition, whereas no change occurred in the levels of the last two enzymes (encoded by pyrE and pyrF) of the pyrimidine pathway . Quantitative nucleotide pool determinations have provided evidence that any individual ribo- or deoxyribonucleoside mono-, di-, or triphosphate of cytosine or uracil is not a repressing metabolite for the pyrimidine biosynthetic enzymes . Other nucleotide derivatives or ratios must be considered.

J Immunol, 1975 Nov, 115(5), 1404 - 8
DNA release as a direct measure of microbial killing . I . Serum bactericidal activity; Friedlander AM; A new method for quantification of microbial killing is presented, based upon the assumption that release of DNA from an organism can be taken as direct evidence of cell death . The assay was applied to measurement of serum bactericidal activity . A "serum-sensitive" Escherichia coli, whose DNA was pre-labeled with {14C} thymidine, released 95 to 100% of its radioactivity upon exposure to human serum for 120 min . This was accompanied by a fall in viability with less than 0.1% of the bacteria surviving . Heating serum to 56 degrees C for 30 min completely abolished both DNA release and killing . Normal serum did not release DNA from a "serum-resistant" . Salmonella typhimurium whereas exposure to ampicillin caused both significant killing and DNA release . This assay is highly specific, sensitive, and rapid.

Cancer Lett, 1975 Nov, 1(2), 91 - 6
Mutagenicity of carcinogenic azo dyes and their derivatives; Yahagi T et al.; The mutagenicity of N,N-dimethyl-4-aminoazobenzene and N-methyl-4-aminoazobenzene and their derivatives was shown on Salmonella typhimurium TA100 and TA98 . S-9 Mix, obtained from rat liver after injection of polychlorinated biphenyl, was abligatory for their mutagenic action . N-Acetoxy-N-methyl-4-aminoazobenzene and N-benzoyloxy-N-methyl-4-aminoazobenzene and their 4'-methoxycarbonyl derivatives were also mutagenic on TA100 and TA98 and did not require metabolic activation by S-9 Mix . It is suggested that the carcinogenic effects of azo dyes may involve modification of DNA.

Zentralbl Bakteriol {Orig A}, 1975 Nov, 233(3), 327 - 34
Reactivity of lipopolysaccharides from various salmonella SR and R chemotypes Ra-Re mutants with concanavalin A; Mayer H et al.; Lipopolysaccharides from different R mutants of Salmonella minnesota and Salmonella typhimurium belonging to chemotypes Ra to Re, as well as from three SR mutants of Salmonella typhimurium were selected for a study of their precipitability with Concanavalin A . Predictions as to the outcome of the reaction could be made since both the chemical structure of the Salmonella R lipopolysaccharides and structural requirements for a positive reaction with Concanavalin A are well established . Precipitation studies in the immuno-electrophoretic assay and in the microcapillary test were carried out with alkali-treated lipopolysaccharides as untreated lipopolysaccharide is too highly aggregated to allow a sufficient migration in agarose layers . Lipopolysaccharides of all mutants--except the SR mutants--were obtained by the phenol/chloroform/petroleum ether method in order to avoid contaminations by glucans or glycogen which are known to occur in phenol/water extracted lipopolysaccharides and which would lead to erroneous results . Additional precipitation studies were carried out with two other lectins of different polysaccharide specificity: Wheat Germ Agglutinin and Soybean Agglutinin . As expected, lipopolysaccharides of chemotypes Ra, Rb1, and RcP- mutants reacted strongly with Concanavalin A, whereas no reaction was demonstrable with lipopolysaccharides of chemotypes Rb2, Rb3, Rd and Re mutants . The lipopolysaccharide of an RcP+ mutant unexpectedly failed to precipitate unless it was dephosphorylated with HF . This artificially prepared RcP-lipopolysaccharide showed a strong reaction, thus demonstrating that negative charges in the direct neighborhood of reactive sugar units as in RcP+ LPS may prevent precipitation with Concanavalin A . No reactivity demonstrable by precipitation could be obtained using either Wheat Germ Agglutinin or Soybean Agglutinin with alkali-treated lipopolysaccharide even of those chemotypes which had the supposedly reactive sugar in a terminal position, such as N-acetyl-D-glucosamine in Ra mutants (Wheat Germ Agglutinin) or D-galactose in Rb2 or Rb3 mutants (Soybean Agglutinin).

J Virol, 1975 Nov, 16(5), 1184 - 90
Host influence on the activity of genes c1 and c3 in regulating the decision between lysis and lysogency in bacteriophage P22; Tokuno SI et al.; A Polymyxin B-sensitive mutant of Salmonella typhimurium (Pox-1) channels all infecting wild-type P22 toward lysogenization . The efficiency of this channeling is sufficiently high that P22c+ (wild type) cannot form plaques on Pox-1; phage mutants defective in repressor synthesis (P22c1, c2, c3) or refractory toward repressor (P22vir B) can form plaques . The lytic growth of all phages which have a functional c1 gene is retarded in Pox-1; this retardation is seen even in phages which cannot make repressor . We present experiments which are consistent with the explanation that the retardation is an exaggeration of a normal regulatory event . In a wild-type host, P22 genes c1 and c3 products, host RNA polymerase, and other host factors (?) interact at a promotor site (c27) IN THE PHAGE DNA . This interaction promotes repressor synthesis and represses transcription of lytic genes . In the mutant Pox-1, a host product involved in viral DNA synthesis and transcription is altered . The altered host product results in stronger retardation of lytic gene transcription . The importance of this interaction in the decision between lysis and lysogeny is discussed . The mutant Pox-1 alters the expression or activity of another phage gene . Gene c3 product is absolutely required for lysogenization in this host, although it is not so required in wild-type S . typhimurium.

J Virol, 1975 Nov, 16(5), 1154 - 60
Altered DNA synthesis in a mutant of Salmonella typhimurium that channels bacteriophage P22 toward lysogeny; Steinberg B et al.; Pox-1, a mutant of Salmonella typhimurium, strongly channels P22 toward lysogeny . Viral DNA synthesis in this slow-growing mutant is delayed to a greater extent than viral protein synthesis . The relative enhancement of c2 repressor synthesis results in much higher repressor/DNA synthesis ratios in Pox-1 than in wild-type cells . This probably accounts for the high frequency of lysogenization.

J Biol Chem, 1975 Oct 10, 250(19), 7593 - 601
Regulation of intracellular adenosine cyclic 3':5'-monophosphate levels in Escherichia coli and Salmonella typhimurium . Evidence for energy-dependent excretion of the cyclic nucleotide; Saier MH Jr et al.; Sugars and other energy sources were found to lower intracellular concentrations of adenosine 3':5'-monophosphate (cyclic AMP) in strains of Escherichia coli and Salmonella typhimurium which were deficient for cyclic AMP phosphodiesterase . This effect required the presence of the specific transport system responsible for entry of that sugar into the cell and depended on the intracellular catabolic enzymes . Metabolizable sugars were more effective than nonmetabolizable sugars in reducing cellular cyclic AMP levels, and this reduction was blocked partially by uncouplers of oxidative phosphorylation . Electron donors such as lactate and ascorbate plus phenazine methosulfate reduced internal cyclic AMP levels in bacterial membrane vesicles which had been preloaded with the cyclic nucleotide . Uncouplers of oxidative phosphorylation, but not arsenate, blocked the energy-stimulated loss of intravesicular cyclic AMP . Employing intact cells, sugars were shown to have two primary effects on cyclic AMP metabolism: (a) they inhibited net synthesis of the cyclic nucleotide while promoting its degradation, and (b) they stimulated efflux of cyclic AMP into the extracellular fluid . While the former effect was elicited by metabolizable and nonmetabolizable sugars alike, stimulation of cyclic nucleotide excretion was only observed with metabolizable sugars . The results suggest that the extrusion of cyclic AMP from the bacterial cell is energy-dependent and is driven by an energized membrane state.

Avian Dis, 1975 Oct-Dec, 19(4), 745 - 60
Influence of age on the serological response of chickens to Salmonella typhimurium infection; Williams JE et al.; After chickens 1-126 days old were infected orally with Salmonella typhimurium, antibody responses were determined by microagglutination (MA) and microantiglobulin (MAG) test procedures . In all groups six weeks old or older, a high and continuing level of salmonella group B antibody was demonstrated by the MAG test but not by the MA test . Serological response was maximal at about 15 weeks or later . Reinoculation with S . typhimurium 129 days after initial infection elevated antibody titers in all groups, and immunological paralysis was evident in only the two youngest groups . S . typhimurium-positive cloacal swabs tended to decline rapidly in all groups; although MAG agglutinin titers remained positive.

J Gen Microbiol, 1975 Oct, 90(2), 203 - 16
Mutations affecting aromatic amino acid transport in Escherichia coli and Salmonella typhimurium; Thorne GM et al.; A genetic locus, aroT, located between chr and the trp operon in Salmonella typhimurium, and similar genes, aroR and aroS, near the trp locus of Escherichia coli, were found to be involved in the transport of aromatic amino acids . Genetic lesions at these loci cause a variable diminution in uptake and accumulation of aromatic amino acids, alanine and glycine compared with the wild type . The F'trp episome carries the aro R locus . Curing an E . coli strain of the F'trp episome which covers a chromosomal deletion from cysB through the trp operon and tonB regions, results in a 60 to 80% decrease in tryptophan uptake . The introduction of F'trp into a trp operon-deleted S . typhimurium of low transport ability restores transportability, suggesting that aroT in this organism may be homologous with aroR in E . coli . In E . coli, tryptophan accumulation is normally increased by prior growth in L-tryptophan, while in S . typhimurium it is repressed . In both genera, the trpR gene appears to have no effect on the tryptophan transport capabilities in response to changes in the concentration of L-tryptophan in the medium . Tryptophan transport in the S . typhimurium F'trp hybrid was subject to repression, while in the E . coli strain which carries F'trp covering the equivalent chromosomal delection, an increase in tryptophan accumulation was shown after growth in L-tryptophan supplemented medium.

J Hyg (Lond), 1975 Oct, 75(2), 203 - 14
Contribution to the study of live streptomycin-dependent Salmonella vaccines: the problem of reversion to a virulent form; Vladoianu IR et al.; The recovery of virulence by means of reversion of a live streptomycin-dependent (Sm D) Salmonella typhimurium vaccine was studied in CD-1 Swiss mice . Initially, a one-step Sm D mutant was obtained from a virulent streptomycin-sensitive (Sm S) S . typhimurium strain . Afterwards, two pools of streptomycin-independent (Sm I) revertants were prepared from the Sm D strain . The virulence of the Sm D strain and of the Sm I revertants was tested intraperitoneally . In the virulence testing the original suspension of the Sm I revertants, as well as their 1st and 10th passages on plain medium, medium+50 mug . streptomycin/ml . and medium+1000 mug . streptomycin/ml . were used . The results show that the Sm D mutant was avirulent, its avirulence being due to an intrinsic, genetic quality . The Sm I revertants, compared to the original Sm S strain, also displayed a lack of virulence . However, afterwards, the Sm I revertants behaved quite differently, according to their subsequent passages . Indeed, there was an increase in virulence after passages on plain medium, whereas similar passages on medium containing the drug, the virulence not only failed to increase, but disappeared almost completely . Moreover, the passages on medium containing 1000 mug . streptomycin/ml . induced a return to the status of drug-dependence . The danger of recovery of virulence by means of revertants is evaluated.

J Am Vet Med Assoc, 1975 Oct 1, 167(7), 551 - 2
Retention of Salmonella typhimurium by certain species of fish and shrimp; Lewis DH; Marine fish (Mugil cephalus, Fundulus heteroclitus, Trachinotus carolinus), lake shrimp (Penaeus setiferus), and channel catfish (Ictalurus lacustris punctatus) were exposed to Salmonella typhimurium and cultured after 2 hours and at daily intervals for 30 days . Salmonella typhimurium was recovered from all exposed animals after 2 hours and for 30 days in all animals except P setifurus . The organisms could not be recovered from those shrimp after the initial sampling period . Apparent salmonellosis developed in certain specimens of M cephalus and T carolinus 10 to 14 days after exposure to S typhimurium.

Infect Immun, 1975 Oct, 12(4), 699 - 705
Effect of glucocorticosteroids on the phagocytosis and intracellular killing by peritoneal macrophages; Zwet TL et al.; The effect of hydrocortisone on the phagocytosis and intracellular killing by mouse peritoneal macrophages in vitro was studied by a method making it possible to measure these processes separately . The results showed that in vivo treatment with 15 mg of hydrocortisone acetate did not significantly decrease the phagocytosis of several bacterial species such as Staphylococcus albus, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa . The killing indexes of normal macrophages for the various microorganisms were found to be significantly different . This may indicate that the bactericidal mechanisms are not uniform for these bacteria . The effect of hydrocortisone on the intracellular killing was also variable . For Staphylococcus albus a normal killing index was found . For the other species of bacterial and for Candida albicans some decrease was found, but this was only significant for Salmonella typhimurium . It is concluded that a decrease host resistance due to glucocorticosterioid treatment is not caused by a direct effect of these drugs on the phagocytosis and intracellular killing by mononuclear phagocytes.

Gann, 1975 Oct, 66(5), 581 - 2
Mutagenicity of 5-nitroacenaphthene in salmonella; Yahagi T et al.; 5-Nitroacenaphthene was proved to be mutagenic on TA100 and TA98 of Salmonella typhimurium with or without metabolic activation by S-9 Mix . A possible metabolite, 5-hydroxyacenaphthene, carcinogenicity of which had not been observed, was non-mutagenic on TA100 and TA98, with or without metabolic activation.

J Bacteriol, 1975 Oct, 124(1), 182 - 9
Regulation of the ammonia assimilatory enzymes in Salmonella typhimurium; Brenchley JE et al.; The regulation of glutamate dehydrogenase (EC 1.4.1.4), glutamine synthetase (EC 6.3.1.2), and glutamate synthase (EC 2.6.1.53) was examined for cultures of Salmonella typhimurium grown with various nitrogen and amino acid sources . In contrast to the regulatory pattern observed in Klebsiella aerogenes, the glutamate dehydrogenase levels of S . typhimurium do not decrease when glutamine synthetase is derepressed during growth with limiting ammonia . Thus, it appears that the S . typhimurium glutamine synthetase does not regulate the synthesis of glutamate dehydrogenase as reported for K . aerogenes . The glutamate dehydrogenase activity does increase, however, during growth of a glutamate auxotroph with glutamate as a limiting amino acid source . The regulation of glutamate synthase levels is complex with the enzyme activity decreasing during growth with glutamate as a nitrogen source, and during growth of auxotrophs with either glutamine or glutamate as limiting amino acids.

Can J Biochem, 1975 Oct, 53(10), 1118 - 21
Cysteine biosynthesis in Salmonella typhimurium: the presence of ATP-sulfurylase and APS-kinase in various cysteine-requiring mutants; Collins JM et al.; Enzymatic tests were performed on a series of cysteine-requiring mutants for the presence of the sulfate activating enzymes . ATP-sulfurylase (sulfate adenylyltransferase EC 2.7.7.4) and APS-kinase (adenylylsulfate kinase EC 2.7.1.25) . The enzymatic products adenosine 5'-{35S}sulfatophosphate and adenosine 3'-phosphate 5'-{35S}sulfatophosphate were identified by paper electrophoresis and measured quantitatively without elution from the paper . Cys mutants mapping in cistrons, A, H, I, J, G, and Ea contain both enzymes . Mutation in the D cistron leads to the loss of ATP-sulfurylase . Mutants mapping in the C cistron lack APS-kinase . Ba, Bb, and Bc mutants lack both enzymes . The control of the synthesis of these enzymes by cysteine was examined . Both enzymes are missing when cells are grown on cysteine.

Mol Gen Genet, 1975 Sep 29, 140(2), 175 - 81
Plasmid-determined alterations of Salmonella typhimurium lipopolysaccharides; Derylo M et al.; Salmonella typhimurium Rc902 infected with derepressed ColIb mutants gave rise to changes in the composition of bacterial lipopolysaccharides (LPS) . Bacteria carrying ColIbdrd7, derepressed in transfer, exhibited a marked decrease in the content of all 0-side-chain sugars of LPS . Similar effect were found upon the introduction of R64-11, also derepressed in transfer . In LPS of S . typhimurium containing ColIbdrd2, derepressed in colicin synthesis, a decrease of abequose content associated with an increase of glucose level was observed . Bacteria carrying the wild-type ColIb, the revertant of a drd mutant to the wild type, or the non colicinogenic strain resulting from the elimination of ColIbdrd2, showed no changes in the sugar composition of LPS.

Mol Gen Genet, 1975 Sep 29, 140(2), 159 - 64
panD, a new chromosomal locus of Salmonella typhimurium for the biosynthesis of beta-alanine; Ortega MV et al.; Three mutants of Salmonella typhimurium LT2, which required either pantothenate or beta-alanine for growth, were obtained after treatment with N-methyl-N'-nitro-N-nitrosoguanidine . Their phenotype was: SM30 Pan-, SM31 Pan- Met-, SM32 Pan- Thi- (requirement for the thiazole-moiety of thiamine) . Neither aspartate, dihydrouracil, nor beta-ureidopropionate replaced beta-alanine as growth factor . By conjugation it was found that the three genetic lesions (Pan-, Met-, Thi-) were located at about minute 128 of the bacterial chromosome . By transduction 63% linkage was found between the Pan and Met loci, and 84% between the Thi and Pan loci . Probably the thiazole auxotrophy was due to a lesion in the thiG locus . The new genetic locus responsible for the synthesis of beta-alanine was named panD.

Mol Gen Genet, 1975 Sep 29, 140(2), 111 - 22
Appearance of transducing particles and the fate of host DNA after infection of Salmonella typhimurium with P22-mutants with increased transducing ability (HT-mutants); Schmieger H et al.; The kinetics of production of transducing particles for different bacterial markers were followed by premature lysis of Salmonella typhimurium cells infected with P22 phages . The were compared for cells infected with wild type phage or with HT-mutants which show increased transduction frequencies . Measuring the sedimentation velocity of bacterial DNA of cells infected with wild type or HT-phages, it was shown that: a) there is no cutting of DNA at random; b) original fragments necessary for packaging host DNA into transducing particles cannot be smaller than 10 phage-genome lengths; c) cutting of transducing fragments leads immediately to the right length; d) there is no loss of precipitable DNA due to phage infection.

J Biol Chem, 1975 Sep 25, 250(18), 7359 - 65
Outer membrane as a diffusion barrier in Salmonella typhimurium . Penetration of oligo- and polysaccharides into isolated outer membrane vesicles and cells with degraded peptidoglycan layer; Nakae T et al.; In Escherichia coli and Salmonella typhimurium, the cell wall that contains both the outer membrane layer and the peptidoglycan layer acts as a barrier of the molecular sieve type for the penetration of uncharged saccharides (G . Decad, T . Nakae, and H . Nikaido (1974) Fed . Proc . 33, 1240) . Here we examined which of the layers of the cell wall limited the size of the penetrating molecules, by studying the penetration of saccharides into (a) cells whose peptidoglycan layer had been destroyed by lysozyme treatment or growth in the presence of penicillin and (b) isolated outer membrane vesicles . We found that peptidoglycan-defective cells were similar to intact, plasmolyzed cells in that they allowed a partial penetration of stachyose (molecular weight 666), but essentially excluded saccharides with molecular weights higher than 900 to 1000 . We also found that the isolated outer membrane acted as a penetration barrier for saccharides . These observations led us to conclude that the outer membrane, rather than peptidoglycan, sets the size limit for the penetration of uncharged, hydrophilic molecules through the E . coli or S . typhimurium cell wall . The isolated outer membrane, however, had an exclusion limit much higher than that found in intact cells . This "leakiness" could be decreased either by the use of mutants producing extremely deficient lipopolysaccharide, or by trypsin treatment of the isolated membrane followed by heating and slow cooling in the presence of Mg2+ . We feel that these observations are consistent with the hypothesis that the resealing of the ruptured outer membrane during the isolation procedure is often incomplete, and that cracks and holes thus generated are responsible for the "leakiness" of the isolated membrane vesicles.

J Biol Chem, 1975 Sep 25, 250(18), 7324 - 31
Studies on the mechanism of inhibition of Salmonella typhimurium by 1,2,4-triazole; Kredich NM et al.; The inhibition of Salmonella typhimurium by 1,2,4-triazole appears to be mediated through an effect on L-cysteine biosynthesis . O-Acetylserine sulfhydrylase A, the final enzyme in the L-cysteine biosynthetic pathway, was found to catalyze a reaction (triazolylase) between O-acetyl-L-serine and 1,2,4-triazole, giving 1,2,4-triazole-1-alanine as a product . In wild type S . typhimurium grown on 4 mM 1,2,4-triazole, 97% of the total O-acetyl-L-serine synthesized in vivo is incorporated into 1,2,4-triazole-1-alanine . 1,2,4-triazole also significantly lowers the levels of several of the enzymes necessary for sulfate reduction . This effect is presumably due to the ability of the inhibitor to lower intracellular concentrations of O-acetyl-L-serine, an inducer of these enzymes . Inhibition of growth is probably caused by L-cysteine starvation, arising from the decreased availability of the L-cysteine precursors, sulfide and O-acetyl-L-serine . Two 1,2,4-triazole-resistant strains bearing mutations in cysK, the structural gene for O-acetylserine sulfhydrylase A, incorporate only small quantities of O-acetyl-L-serine into 1,2,4-triazole-1-alanine in vivo . In vitro studies, using purified preparations of O-acetylserine sulfhydrylase A, revealed greater losses of triazolylase activity than sulfhydrylase activity in the enzymes from both cysK mutants . Resistance to 1,2,4-triazole apparently can arise from mutations leading to a preferential loss of triazolylase activity or from mutations which diminish both activities to the extent that high concentrations of O-acetyl-L-serine and sulfide accumulate behind the sulfhydrylase reaction.

J Biol Chem, 1975 Sep 25, 250(18), 7492 - 500
Studies of the quaternary structure and the chemical properties of phosphoribosylpyrophosphate synthetase from Salmonella typhimurium; Schubert KR et al.; Phosphoribosylpyrophosphate (PRPP) synthetase (EC 2.7.6.1) was purified to virtual homogeneity from Salmonella typhimurium cells by a modification of previously published procedures . The molecular weight of the subunit was determined to be 31,000 +/- 3,000 by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and sedimentation equilibrium analysis of the enzyme dissolved in 6 M guanidine hydrochloride . The amino acid composition of the enzyme was determined . Proline was identified as the only NH2-terminal residue . PRPP synthetase is apparently composed of identical or nearly identical subunits . NATIVE PRPP synthetase exists in multiple states of aggregation under all conditions . However, two predominant states were demonstrated under certain conditions . A form with molecular weight of 320,000 +/- 20,000 was found at pH 7.5 in the presence of MgATP . At pH 8.2 to 8.6, with or without MgATP, the predominant form corresponded to a molecular weight of 150,000 to 200,000; sedimentation equilibrium and velocity analysis indicated 160,000 +/- 15,000 as the most reliable molecular weight . More highly aggregated forms were observed at 4 degrees and higher protein concentrations . Removal of inorganic phosphate from PRPP synthetase by dilution or dialysis resulted in disaggregation . The fundamental unit of PRPP synthetase appears to consist of five (or possibly six) subunits, which can associate to form a dimer (10 or 12 subunits) and more highly aggregated forms . A pentameric subunit structure is consistent with the multiple species resolved by electrophoresis of the native enzyme in discontinuous polyacrylamide gel systems . Visualization of PRPP synthetase by negative staining with uranyl acetate and electron microscopy revealed fields of very asymmetric molecules, the dimensions of which corresponded to the M = 160,000 form . Dimers and higher aggregates of this unit were also seen . An unusual model, in which the five subunits are asymmetrically arranged, accounts very well for the electron microscopic appearance of the enzyme . The tendency of the enzyme to aggregate is viewed as a consequence of the unsatisfied bonding regions of the fundamental asymmetric unit.

Biochim Biophys Acta, 1975 Sep 22, 403(1), 47 - 57
Regulation of GMP reductase in Salmonella typhimurium; Benson CE et al.; The levels of guanosine 5'-phosphate reductase (EC 1.6.6.8) in Salmonella typhimurium appear to be modulated by changes in the ratio of the adenine and guanine nucleotide pools . Alterations of this ratio may be induced by high levels of guanosine in the culture medium or by genetic lesions in one of several purine interconversion enzymes, such as pur A or pur B mutants . The induction of the reductase requires transcription and translation processes and, in contrast to earlier observation with Escherichia coli, is not dependent on cyclic adenosine 3',5'-phosphate or the cyclic adenosine 3',5'-phosphate receptor protein.

J Biol Chem, 1975 Sep 10, 250(17), 6769 - 78
Mutagenesis of certain activated carcinogens in vitro associated with genetically mediated increases in monooxygenase activity and cytochrome P 1-450; Felton JS et al.; A bacterial mutagenesis assay and genetic differences in microsomal CO-binding cytochromes were combined in vitro to evaluate the metabolic activation of several known carcinogens to frameshift mutagens . With the use of liver fractions from C57BL/6N and DBA/2N control mice and mice treated in vivo with 3-methylcholanthrene, beta-naphthoglavone, phenobarbital, or 2,3,7,,-tetrachlorodibenzo-p-dioxin, the in vitro mutagenicity of 3-methylcholanthrene, 6-aminochrysene, and 2-acetylaminofluorene --but not benzo{a}pyrene==is closely associated with the genetically mediated difference in both aromatic hydrocarbon-inducible aryl hydrocarbon (benzo{a}pyrene) hydroxylase activity and new cytochrome P1-450 formation; such an association between 7,12-dimethylbenz{a}anthracene or benz{a}anthracene activation to mutagens in vitro and these genetic differences between C57BL/6N and DBA/2N mouse strains in uncertain . The Salmonella typhimurium histidine mutant TA1538 is more effective than tester strains TA1537 and TA1535 in the determination of 3-methylcholanthrene mutagenesis in vitro . The relationships between the histidine revertant rate as a function of both liver protein concentration per plate and mutagen concentration per plate are illustrated for 3-methylcholanthrene, benzo{a}pyrene, 6-aminochrysene, and 2-acetylaminofluorene . With the use of offspring from the appropriate genetic crosses, the aromatic hydrocarbon-inducible hydroxylase activity appears to be expressed as an autosomal dominant trait, whereas the mutagenesis of 3-methylcholanthrene in vitro appears to be expressed additively; this apparent discrepancy probably reflects different proportional amounts of phenolic benzo{a}pyrene, compared with mutagenic 3-methylcholanthrene metabolites, formed by the monooxygenase(s) . 3-Methylcholanthrene, 6-aminochrysene, and 2-acetylaminofluorene--but not benzo{a}pyrene--are each more mutagenic in vitro per molecule of cytochrome P1-450 than per molecule of CO-binding cytochrome other than P1450 . Diethylmaleate, a compound which depletes flutathione content in liver, and 1,1,1-trichloropropene-2,3-epoxide, an inhibitor of epoxide hydrase (EC 4.2.1.63), were also studied in vitro . Diethylmaleate, and especially 1,1,1-trichloropropene-2,3-epoxide, increases the mutagenicity of benzo{a}pyrene, whereas no increases occur with 3-methylcholanthrene, 6-aminochrysene, or 2-acetylaminofluorene activation to mutagens in vitro . Both diethylmaleate and 1,1,1-trichloropropene-2,3-epoxide cause decreases in 2-acetylaminofluorene mutagenesis in vitro when liver fractions from phenobarbital-treated mice are used.

J Biol Chem, 1975 Sep 10, 250(17), 7078 - 80
Coordinate regulation of adenylate cyclase and carbohydrate permeases by the phosphoenolpyruvate:sugar phosphotransferase system in Salmonella typhimurium; Saier MH Jr et al.; Adenylate cyclase (EC 4.6.1.1) and several carbohydrate permeases are inhibited by D-glucose and other substrates of the phosphoenolpyruvate:sugar phosphotransferase system . These activities are coordinately altered by sugar substrates of the phosphotransferase system in a variety of bacterial strains which contain differing cellular levels of the protein components of the phosphotransferase system: Enzyme I, a small heat-stable protein, and Enzyme II . It is suggested that the activities of adenylate cyclase and the permease proteins are subject to allosteric regulation and that the allosteric effector is a regulatory protein which can be phosphorylated by the phosphotransferase system.

Mol Gen Genet, 1975 Sep 8, 139(4), 277 - 84
Location of the argR gene on the chromosome of Salmonella typhimurium; Kelln RA et al.; The regulatory gene (argR) for the arginine biosynthetic pathway has been located at 106 min on the chromosome of S . typhimurium . In addition, the location of the gene specifying cytosine deaminase (cod) has been more precisely determined.

Proc Natl Acad Sci U S A, 1975 Sep, 72(9), 3453 - 7
Histidine regulation in Salmonella typhimurium: an activator attenuator model of gene regulation; Artz SW et al.; An activator-attenuator model of positive control, a s opposed to the classic repressor-operator model of negative control, is proposed for the major operon-specific mechanism governing expression of the histidine gene cluster of Salmonella typhimurium . Evidence for this mechanism is derived from experiments performed with a coupled in vitro transcription-translation system, as well as with a minimal in vitro transcription system {Kasai, T . (1974) Nature 249, 523--527} . The product (G enzyme, or N-1-{5'-phosphoribosyl}adenosine triphosphate:pyrophosphate phosphoribosyltransferase; EC 2.4.2.17) of the first structural gene (hisG) of the histidine operon is not involved in the positive control mechanism . However, a possible role for G enzyme as an accessory negative control element interacting at the attenuator can be accommodated in our model . The operon-specific mechanism works in conjunction with an independent mechanism involving guanosine 5'-diphosphate 3'-diphosphate (ppGpp) which appears to be a positive effector involved in regulating amino-acid-producing systems, in general {Stephens, J.C., Artz, S.W . & Ames, B.N . (1975) Proc . Nat . Acad . Sci . USA, in press}.

Am J Epidemiol, 1975 Sep, 102(3), 257 - 62
An outbreak of salmonellosis propagated by person-to-person transmission on an Indian reservation; Loewenstein MS; Between December 21, 1969, and April 14, 1970, 44 symptomatic cases of Salmonella typhimurium gastroenteritis occurred among the approximately 2500 Sioux Indians of the Lake Traverse Reservation in South Dakota . Twenty-five cases were confirmed by positive stool culture . All 19 cases not confirmed by culture had diarrhea and were epidemiologically associated with the culture-proven cases . Fourteen of these were discovered during the course of the investigation and had not been cultured previously . Twelve cases were hospital-acquired and 32 community acquired . Both the nosocomial and community-acquired infections occurred randomly during the 17-week span of the epidemic . Despite extensive investigation, no common exposure was discovered . The hospital-acquired infections all occurred in patients who shared a room or nursing personnel with patients who had active disease, or were born of a woman with active disease at the time of parturition . Twenty-nine of the 32 community acquired cases were linked to each other by person-to-person contact . This epidemic is the first documented outbreak of non-institutional salmonellosis propagated by person-to-person transmission.

J Bacteriol, 1975 Sep, 123(3), 792 - 805
Behavior of a hybrid F' ts114 lac+, his+ factor (F42-400) in Klebsiella pneumoniae M5a1; Rao RN et al.; Episome F' ts114 lac+, his+ (F42-400) was transferred from Salmonella typhimurium to Klebsiella pneumoniae . From the progeny, a strain of K . pneumoniae able to retransfer the episome was obtained . The His+ phenotype in this strain is temperature sensitive . Escherichia coli female-specific phages phiII, W31, and T3 were shown to plate on K . pneumoniae . From phiII we obtained two derivatives; phiIIK, which plates only on K . pneumoniae, and phiIIE, which plates only on E . coli . Growth of phages T3 and phiIIK was inhibited by F42-400 in K . pneumoniae . Growth in presence of acridine orange in a defined medium at 40 C resulted in a high level of curing . The frequency of His+ cells after growth in acridine orange at 40 C was 0.001% . An extensive search to detect chromosome mobilization by F42-400 in K . pneumoniae, under different experimental conditions, was negative . We cannot exclude the possibility that the low transfer efficiencies prevented our detection of chromosome mobilization . A search among temperature-resistant, acridine orange-curing-resistant, or galactose-resistant derivatives of the K . pneumoniae donor strain failed to reveal any chromosome transfer . Our failure to detect Hfr's may be a result of: (i) the peculiarity of episome F42-400, (ii) the peculiarity of K . pneumoniae chromosome, or (iii) low transfer efficiency . K . pneumoniae-modified F42-400 and phage 424 were restricted by E . Coli K-12 . E . coli K-12-modified episome F42-400 and phage 424 were restricted by K . pneumoniae . E . coli C failed to restrict F42-400 modified with K . pneumoniae specificity . The ability of K . pneumoniae to accept F42-400 is less, by about a factor of 50, than that of E . coli C . As an explanation for the differences in the behavior of E . coli C and K . pneumoniae in ability to receive F42-400 it was suggested that recipient bacteria have specific sites for interaction with the F-pilus tip; these are present in E . Coli C, leading to high transfer efficiency, whereas they may not be present (or if present, are not accessible) in K . pneumoniae, leading to low transfer efficiency.

J Bacteriol, 1975 Sep, 123(3), 779 - 91
Isolation of a hybrid F' factor-carrying Escherichia coli lactose region and Salmonella typhimurium histidine region, F42-400 (F' ts114 lac+, his+): its partial characterization and behavior in Salmonella typhimurium; Rao RN et al.; Episome F' ts114 lac+ (F42-114) was transferred into Salmonella typhimurium carrying an F'his+ (FS400) episome, and fused episome F' ts114 lac+, his+ (F42-400) was obtained . Episome F42-400 could be transferred to S . typhimurium, Escherichia coli and Klebsiella pneumoniae . Identification of the episome was based on: (i) temperature sensitivity of the Lac+ and His+ phenotypes; (ii) the fact that F- segregants, obtained after temperature curing or acridine orange curing, were simultaneously Lac- and His-; and (iii) linkage of lac+ with his+ in episomal transfers to E . coli and S . typhimurium . The frequency of episome transfer was influenced by the genotype of the donor . Plasmid LT2, prevalent in S . typhimurium LT2 strains, was suggested to be responsible for the low fertility of S . typhimurium donors . Episome F42-400 was capable of chromosome mobilization, and the extent of chromosome mobilization was not influenced by the presence or absence of the histidine region on the donor chromosome . Growth in a defined medium with acridine orange was able to cure F42-400 . The frequency of curing was increased (the frequency of His+ cells was 0.0001%) if the cells were grown at 40 C in the presence of acridine orange . Selection for temperature-resistant Lac+, His+ derivatives in a strain without histidine deletion yielded Hfr strains . However, similar and stronger selections in strains without the chromosomal histidine region failed to yield Hfr strains . Our inability to obtain Hfr's in strains without the chromosomal histidine region was explained by assuming that the episome F42-400 has lost the F sites involved in integration into the S . typhimurium chromosome.

J Bacteriol, 1975 Sep, 123(3), 1254 - 64
Deletions fusing the hisG and hisD genes in Salmonella typhimurium; Ino I et al.; Frameshift mutation hisD497 occurs in the operator-proximal portion of the Salmonella typhimurium gene coding for the dimeric protein, L-histidinol dehydrogenase (HDH) . Rare revertants of hisD497 are deletions fusing the hisD gene to the adjacent preceding structural gene, hisG (adenosine 5'-triphosphate-PR transferase) . HDH purified from one revertant, hisGD4908, contains subunits of approximately normal molecular weight but with no clearly demonstrable unique amino-terminal sequence . We propose that a combined inactive G-D polypeptide is synthesized and then cleaved at a number of closely juxtaposed sites by endoproteolytic activity . At least some of the resulting fragments then participate in formation of active HDH dimers.

Cancer Res, 1975 Sep, 35(9), 2461 - 8
Metabolism of cigarette smoke condensates by human and rat homogenates to form mutagens detectable by Salmonella typhimurium TA1538; Hutton JJ et al.; Nineteen fractions of whole condensate of smoke from the University of Kentucky Reference Cigarette IRI were tested for mutagenicity in vitro using a bacterial indicator system . As little as 25 mug of the active fractions were mutagenic toward histidine-requiring Salmonella typhimurium TA1538, if the condensates were incubated in the presence of rat or human liver homogenates of lung were relatively inactive . Homogenates from livers of rats that had been treated with 3-methylcholanthrene converted condensates to mutagens more efficiently than did liver homogenates from man or from normal or phenobarbital-treated rats . Use of homogenates from animals treated with 3-methylcholanthrene gave much more reproducible results in smoke fraction assays because larger numbers of revertants were obtained, and dose-response curves were linear over the range 25 to 250 mug condensate . The linear dose-response curves permitted quantitative comparison of the various fractions . The mutagenicity per mg of basic fractions of whole smoke condensate is very high and that of neutral polycyclic hydrocarbons is very low . Because of the exquisite preferential sensitivity of the TA1538 test system to polycyclic amines and insensitively to alkyl polycyclics, there is a poor quantitative correlation between mutagenicity and carcinogenicity, as measured by skin painting or in vitro cell transformation . There is substantial evidence that many carcinogens are mutagens but that most of these compounds require metabolism before they are biologically active . If further development improves the sensitivity of the bacterial testing system to mutagenic derivatives of alkyl polycyclic and heteropolycyclic hydrocarbons, it may provide a convenient, rapid, quantitative, and inexpensive bioassay for the detection of potentially carcinogenic substances in tobacco smoke condensates.

Cancer Res, 1975 Sep, 35(9), 2307 - 14
Factors affecting metabolism and mutagenicity of dimethylnitrosamine and diethylnitrosamine; Frantz CN et al.; For exploration of the factors affecting dimethylnitrosamine (DMN) mutagenicity, for gathering of information on the metabolism of DMN, a frequently used and relatively well-understood carcinogen, and for explanation of metabolic variations in DMN carcinogenicity, parallel in vitro assays of the microsomal activation of DMN to a mutagen and of DMN demethylation were performed . Salmonella typhimurium G46 reversions to histidine independence increase linearly with time of incubation for 30 min . At low concentrations of microsomal protein, increases in protein yield a more than proportional increase in mutations . Increasing DMN concentration saturates the enzyme, yielding less demethylation and fewer mutations proportionately . Mutagenesis is completely inhibited by 1 mM 2-diethyl-aminoethyl-2,2-diphenylvalerate . When both DMN and microsomal protein are varied at high concentrations, there is a simple linear relationship between mutagenicity and DMN demethylase activity . Thus DMN demethylase activity may be the primary controlling factor in the metabolism of DMN to a mutagen, and probably to a carcinogen; other simultaneous pathways of DMN metabolism proportional to demethylation have not been ruled out . Induction with both phenobarbital and 3-methylcholanthrene (3-MC) increased rat and mouse liver DMN demethylase activity . Mouse liver microsomes from the C57BL/6 strain demethylate DMN at a markedly lower rate than do microsomes from the C3H strain, but after 3-MC induction the relationship is reversed . Strain differences in activation of DMN were not found in the activation of diethylnitrosamine to a mutagen . Hepatic dealkylation of DMN and diethylnitrosamine to active mutagenic metabolites is increased in both rats and mice by both 3-MC and phenobarbital induction, which is in contrast to the findings of others that 3-MC and phenobarbital induction, which is in contrast to the findings of others that 3-MC decreases the incidence of DMN-induced hepatic tumors in rats, and phenobarbital decreases the incidence of diethylnitrosamine-induced hepatic tumors in mice.

Poult Sci, 1975 Sep, 54(5), 1388 - 94
Destruction of Salmonella on poultry meat with lysozyme, EDTA, x-ray, microwave and chlorine; Teotia JS et al.; Lysozyme, ethylenediaminetetracetic acid, chlorine, x-irradiation and microwaves were used in experimental attempts to eliminate Salmonella senftenberg 775W or Salmonella typhimurium from turkey drumsticks and whole carcasses . Turkey drumsticks or whole carcasses were artificially contaminated with S . senftenberg 775W or S . typhimurium in concentrations ranging between 5 X 10(5) to 8 X 10(5) viable cells per ml . of contaminating fluid . After each treatment, samples were cultured, plated, and tested according to standard methods to determine the susceptibility of Salmonella organisms to the particular treatment . A 0.1 percent solution of lysozyme eliminated the S . senftenberg 775W at 22 degrees C . within three hours . A 0.5 percent solution of ethlenediaminetetracetic acid failed to destroy the test organism under the same conditions . Eighty thousand rads of X-ray eliminated the test organism on turkey drumsticks but failed to remove it from whole turkey carcasses . Microwaves eliminated the S . senftenberg 775W in 150 seconds from turkey drumsticks and ten minutes from broiler chicken carcasses . Aqueous solutions containing 3400 and 2125 p.p.m . chlorine failed to destroy the test organism on turkey drumsticks at 21 degrees C . in 9 and 24 hours . None of the treatments changed the appearance of the skin or meat, except microwaves produced a partially-cooked appearance . Chlorine produced off-color drumsticks.

Cancer Lett, 1975 Sep, 1(1), 39 - 42
Testing of some benzidine analogues for microsomal activation to bacterial mutagens; Garner RC; Analogues of benzidine were assayed for mutagenic activity towards Salmonella typhimurium TA 1538 in the presence and absence of a liver enzyme preparation . Purified 3,3'-dichlorobenzidine and the technical grade material had some direct mutagenic activity, but this was increased over 50-fold by addition of a liver mixed function oxidase preparation . In the presence of the liver preparation, 3,3'-dichlorobenzidine was approximately 10 times more active than benzidine, while 3,3',5,5'-tetrafluorobenzidine was of approximately equipotency . On the other hand, 3,3',5,5'-tetramethylbenzidine had no mutagenic activity alone or in conjunction with a liver preparation . 3,3'-Dianisidine had slight mutagenic activity in the presence of liver but none in its absence.

Rev Asoc Argent Microbiol, 1975 Sep-Dec, 7(3), 91 - 6
Lysis of a temperature conditional thiamineless mutant of Salmonella typhimurium by glucose and other hexoses; Parada JL et al.; The SM-3 mutant of Salmonella typhimurium was isolated as streptomycin resistant and temperature conditional thiamine auxotroph . At 37 C it required thiamine, although it behaves as a leaky mutant at this temperature in minimal liquid medium . At 30 degrees C it was able to growth without thiamine . In minimal-glucose-aminoacids at 37 C after an initial growth, cellular lysis occurred . The same happened with other hexoses, but it was not observable when glycerol or lactate were used as carbon source . Microscopic examination showed clumps of cellular debris, empty bagshapes and swelling of microorganisms, suggesting a cell wall defect . Sucrose 0.5 M protected SM-3 cells from osmotic fragility . At 30 C growth was normal and at 37 C in presence of exogenous thiamine full growth without bacteriolysis was obtained . Preliminary experiments of bacterial conjugation allowed the identification of a new locus involved in thiamine biosynthesis which was tentatively mapped in the pur A - pro B region of the chromosomal map of S . typhimurium.

Tsitol Genet, 1975 Sep-Oct, 9(5), 400 - 3
{Study of the mutagenic activity of mazheptil}; Revazova IuA et al.; Mutagenic activity of the psychotropid drug--majeptil was studied . Majeptil does not induce gene mutations on Salmonella typhimurium and chromosomal aberrations in mice bone marrow cells in vivo . It is shown that majeptil increase the level of chromosome aberrations in the culture of human peripheral blood lymphocytes . It is also active in the dominant lethal test on mice.

J Bacteriol, 1975 Sep, 123(3), 1000 - 5
Soluble and membrane-bound aspartate-binding activities in Salmonella typhimurium; Aksamit RR et al.; The specificities of the soluble and membrane aspartate-binding activities were compared with each other and with the specificity of aspartate chemotaxis and were found to be distinct . The soluble aspartate-binding protein was purified to homogeneity and had a molecular weight of 30,000 . The dissociation constant was 10(-6) M for aspartate, and the protein bound glutamate, cysteic acid, and 2-amino-3-phosphonopropionate . Aspartate transport was inhibited by cysteic acid.

Infect Immun, 1975 Sep, 12(3), 687 - 93
Characterization of monkey peripheral neutrophil granules during infection; Rausch PG et al.; Rhesus monkey (Macaca mulatta) neutrophils were shown to contain the azurophilic granule maker enzymes myeloperoxidase and beta-glucuronidase but were deficient in the specific granule markers alkaline phosphatase (AKP) and lysozyme . Isopycnic centrifugation of leukocyte homogenates on linear sucrose gradients resulted in cosedimentation of myeloperoxidase and beta-glucuronidase with an equilibrium density of 1.18 . After an intravenous inoculation of monkeys with Salmonella typhimurium AKP activity became marked, whereas that of beta-glucuronidase decreased and myeloperoxidase remained unchanged . Lysozyme was undetected throughout the course of the experiment, but was present in oil-induced peritoneal macrophages and peripheral mononuclear cells . The induced AKP exhibited partial latency and had an equilibrium density of 1.15 . It is unclear, however, whether the induced AKP is associated with specific granules or cytoplasmic membranes . Hence, while these data are consistent with the presence of azurophilic granules in polymorphonuclear neutrophils from infected monkeys, the presence of specific granules in polymorphonuclear neutrophils of both uninfected and infected monkeys remains moot.

J Bacteriol, 1975 Sep, 123(3), 878 - 87
Tryptophan biosynthesis in Salmonella typhimurium: location in trpB of a genetic difference between strains LT2 and LT7; Stuttard C; Salmonella typhimurium prototrophs carrying a trpR mutation synthesize tryptophan biosynthetic enzymes constitutively . When feedback inhibition of anthranilate synthetase but not 5'-phosphoribosylpyrophosphate phosphoribosyltransferase activity was by-passed by growing cells on media supplemented with anthranilic acid, all trpR prototrophs overproduced and excreted tryptophan . However, the rate of tryptophan production depended on both the ancestry of the trpR strain and the integrity of its trpA gene . Prototrophs with trp genes derived from S . typhimurium strain LT2 produced tryptophan more efficiently than those with trp genes derived from strain LT7 . This strain difference was cryptic insofar as it did not affect the growth rate; it was revealed only as a rate-limiting step in the constitutive biosynthesis of tryptophan in the presence of anthranilic acid, and was due to a lesion in the LT7-derived trpB gene . Strains with LT7-derived trp genes bearing a deletion in trpA produced tryptophan as readily as LT2 trpR prototrophs . This indicated that LT7-specific 5-phosphoribosylpyrophosphate phosphoribosyltransferase must be aggregated with the trpA gene produce to give an observable reduction of constitutive tryptophan production . The discovery of this strain difference has particular implications for studies involving the activities of trpA and B genes and their products in S . typhimurium and may have general significance for other studies involving different strains of Salmonella.

J Bacteriol, 1975 Sep, 123(3), 851 - 4
pyrR identical to pyrH in Salmonella typhimurium: control of expression of the pyr genes; Justesen J et al.; Mutants of Salmonella typhimurium showing constitutive synthesis of the pyrimidine biosynthetic enzymes coded for by the pyrA-F genes (G . A . O'Donavan and J . C . Gerhart, 1972) have been reinvestigated . The high rate of expression of the pyrB-F genes in these mutants as well as their pyrimidine excretion is shown to be due to mutations in the gene pyrH encoding uridine 5'-monophosphate kinase . Thus, the term pyrR used for these mutants should be replaced by the designation pyrH.

Mol Gen Genet, 1975 Aug 27, 139(3), 213 - 31
Integrative suppression of a dnaA mutation in Salmonella typhimurium; Bagdasarian M et al.; Integrative suppression of a dnaA mutation in Salmonella typhimurium may result from the integration of F'lac or F'his into the chromosome in the left hand side of the chromosomal map . The suppressed revertants resulting from this integration do not contain DNA of the F' elements in the covalently closed circular (CCC)1 form but still contain the CCC DNA of the cryptic LT2 plasmid . Two suppressed revertants isolated from dnaA/F- strains were found in which the suppression of dnaA character was accompanied by the loss of CCC DNA from the cell lysates . From one of these revertants a segregant was isolated in which the return to the dnaA phenotype was accompanied by the reappearance of CCC DNA in the cell lysate . It is suggested that the cryptic plasmid may integrate into the chromosome of S . typhimurium and this integration may result in suppression of the dnaA mutation . Additional evidence suggesting that the cryptic plasmid controls its own initiation of replication independently of the function of the chromosomal dnaA gene is supplied by the results of the determination of incorporation of labelled thymidine into CCC DNA of the dnaA1 strain at the nonpermissive temperature.

Mol Gen Genet, 1975 Aug 27, 139(3), 177 - 88
DNA restriction and modification systems in Salmonella . III . SP, a Salmonella potsdam system allelic to the SB system in Salmonella typhimurium; Bullas LR et al.; By screening 42 Salmonella strains with P3, a temperate bacteriophage with an unusually wide host range, five new DNA restriction and modification systems (R-M systems) were identified in five different serotypes in Kauffmann-White group C . One of these systems, SP, in a Pl-sensitive strain of S . potsdam, was analyzed genetically by Pl transduction methods in which SP was transferred into S . typhimurium and C . coli/S . typhimurium hybrids . It was found that the genes of the SP system were allelic and functionally homologous to the genes of the SB system of S . typhimurium.

Eur J Biochem, 1975 Aug 15, 56(2), 369 - 74
Histidyl-tRNA synthetase from Salmonella typhimurium: specificity in the binding of histidine analogues; Lepore GC et al.; The topography of the active site of histidyl-tRNA synthetase has been investigated by determining Ki values for a variety of structural analogues of histidine, using the ATP-PPi exchange and tRNA aminoacylation reactions . Using these kinetic constants it has been possible to have a measure of the relative binding affinity of the enzyme for the histidine analogues . The following conclusions have been drawn: (a) the enzyme is stereospecific in the formation of aminoacyl-tRNA complexes, since the D-isomer of histidine does not influence the two reactions; (b) the carboxyl group is not required for binding; (c) bulky derivatives of the carboxyl group prevent the molecules from binding to the enzyme; (d) the amino group permits a good binding affinity; (e) the length of the ring side chain plays a very important role as point of attachment to the enzyme; (f) the kinds of heteroatoms on the ring determine the inhibitory properties of the analogues.

J Bacteriol, 1975 Aug, 123(2), 557 - 69
Intrinsic and extrinsic light responses of Salmonella typhimurium and Escherichia coli; Taylor BL et al.; Exposure to intense light in the region between 390 and 530 nm has been shown to have three effects on the motility of Salmonella typhimurium and Escherichia coli . Short pulses of light initiate continuous tumbling . Longer exposures to light induce smooth swimming, and prolonged exposures induced paralysis . The tumbling response is intimately connected with the chemical gradient-sensing apparatus of the bacterium and can be overcome by strong temporal gradients of attractant . Some mutants of S . typhimurium which are defective in the tumble-generating mechanism for chemotaxis are also unable to tumble in intense light . This intrinsic light effect can be mimicked by the addition of external dyes (the classical photodynamic effect), but it can be shown that the two phenomena are distinct . The extrinsic (photodynamic) effect can be inhibited by histidine or by anaerobic conditions, whereas the intrinsic effect is not . The observation that the extrinsic effect can also produce the three types of light responses listed above suggests a common pathway after an intial event on either an endogenous or an externally added photoreceptor.

Proc Natl Acad Sci U S A, 1975 Aug, 72(8), 3176 - 80
Mutagenic and cytotoxic activity of benzol{a}pyrene 4,5-, 7,8-, and 9,10-oxides and the six corresponding phenols; Wood AW et al.; The benzo{a}pyrene 4,5-, 7,8-, and 9,10-oxides and the six corresponding phenols (4-, 5-, 7-, 8-, 9-, and 10-hydroxybenzo{a}pyrene) have been tested for mutagenic and cytotoxic activity in bacteria and in a mammalian cell culture system . Benzo{a}pyrene 4,5-oxide (K-region) was highly mutagenic in two histidine-dependent strains (TA1537 and TA1538) of Salmonella typhimurium which detect frameshift mutagens . In contrast, benzo{a}pyrene 7,8- and 9,10-oxides were less than 1% as mutagenic as the 4,5-oxide . Benzo{a}pyrene 7,8- and 9,10-oxides were unstable in aqueous media, whereas the 4,5-oxide was stable for several hours . This difference in stability could not account for the different mutagenic activities of the three arene oxides . The benzo{a}pyrene oxides were inactive in a strain (TA1535) that is reverted by base pair mutagens such as N-methyl-N'-nitro-N-nitrosoguanidine or in a strain (TA1536) that detects framshift mutagens similar to the acridine half-mustard ICR-191 . Benzo-{a}-pyrene and the six phenols were all stable in aqueous media, but they had little or no mutagenic activity in any of the four Salmonella strains . Conversion of 8-azaguanine-sensitive Chinese hamster V79 cells to 8-azaguanine-resistant variants was increased by benzo{a}pyrene 4,5-oxide, whereas the 9,10-oxide was considerably less active . Benzo{a}pyrene and the other derivatives had little or no effect . Benzo{a}yrene 4,5-oxide was more cytotoxic to the Chinese hamster V79 cells than the 7,8- and 9,10-oxides, while 8-hydroxybenzo{a}pyrene was the most cytotoxic of the six phenols.

J Gen Microbiol, 1975 Aug, 89(2), 265 - 76
Temporary expression of flagellar phase-1 in phase-2 clones of diphasic Salmonella; Iino T et al.; Diphasic Salmonella strains, Salmonella typhimurium TM2, S . abony SW803 and their derivatives differing in flagellar shape and antigen type, were found to produce copolymer segments of phase-1 and phase-2 flagellins among flagella in phase 2, except for a strain which is non-flagellate in phase 1 . The copolymer segments were not detected in phase-1 clones of any of the strains . The wave-forms of the copolymers are homologous with those of the copolymer filaments obtained by in vitro reconstitution of the corresponding phase-1 and phase-2 flagellins . Thus, in the mutant producing normal flagella in phase 1 and straight ones in phase 2, copolymer segments with curly or small waves appear among the straight filaments . Formation of the copolymers was attributed to temporary derepression of the structural gene for phase-1, flagellin, HI, in phase 2 . Copolymerization occurred in a fraction of the phase-2 cell population at late exponential and early stationary phase in nutrient broth cultures . When a phase-2 cell was temporarily derepressed, the copolymers formed almost simultaneously in every growing flagellar filament of the cell . Their formation continued for a short period until the supply of phase-1 flagellin was exhausted after re-establishment of repression . This period was estimated to be 7-7 min on average, fluctuating between 4 and 13 min in a cell population of a straight flagellar mutant whose generation time was 55 min in late exponential phase.

Infect Immun, 1975 Aug, 12(2), 411 - 8
In situ separation of bacterial trapping and killing functions of the perfused liver; Moon RJ et al.; CF-1 mice cleared and killed 80% of a 1.2 x 10(9) intravenous dose of Salmonella typhimurium after 30 min . The perfused mouse liver trapped 70% of a similar dose of S . typhimurium in a single pass, but in the perfusion model no significant killing of the trapped organisms was observed . The perfused rat liver also avidly trapped bacteria . Because of its larger size, we have been able to devise techniques to experimentally distinguish between the bacterial trapping and killing functions of this organ . When the liver was washed free of blood with sterile M-199, over 70 to 80% of a 10(6) to 10(10) dose of viable S . typhimurium was trapped after a single pass, but no significant bacterial killing was observed . When blood or plasma was added to the perfusion medium, over 50% of the trapped bacteria were killed in 15 to 30 min . Phase contrast and electron micrographs of perfused livers showed extensive extracellular trapping of bacteria in the sinusoids . Our data show that humoral factors are apparently not necessary for efficient trapping of live Salmonella by the perfused rat liver but are an absolute requirement for bacterial activity of the organ.

J Bacteriol, 1975 Aug, 123(2), 761 - 4
Amino-terminal sequences of indoleglycerol phosphate synthetase of Escherichia coli and Salmonella typhimurium; Li SS et al.; The partial sequences of the first 40 residues of indoleglycerol phosphate synthetase of Escherichia coli and Salmonella typhimurium were determined, and three amino acid differences were observed among the 38 residues compared.

J Bacteriol, 1975 Aug, 123(2), 570 - 9
Regulation of catalase synthesis in Salmonella typhimurium; Finn GJ et al.; The specific activity of catalase in Salmonella typhimurium and other enteric bacteria decreased during the logarithmic phase of growth and increased at the onset and during the stationary phase . The increase in catalase synthesis at the end of the exponential phase in S . typhimurium cells coincided with the lowest pH value reached by the culture . Maintenance of the pH at a constant neutral value did not alter the typical pattern of synthesis in contradiction of the results previously reported (McCarthy and Hinshelwood . 1959) . A sudden decrease in the pH value of an S . typhimurium culture during exponential growth by addition of HC1 did not cause an alteration in the catalase synthesis pattern . Addition of hydrogen peroxide to S . typhimurium cultures within the range 1 muM TO 2MM during the exponential growth phase stimulated catalase synthesis . The extent of catalase synthesis depended on the concentration of hydrogen peroxide; the maximum stimulation was observed at 80 muM . Increased catalase synthesis was not detected for 10 to 15 min after hydrogen peroxide addition . Hydrogen peroxide was produced by S . typhimurium cultures during the exponential and stationary growth phases . However, no direct relationship between hydrogen peroxide accumulation and synthesis of catalase was observed.

J Gen Microbiol, 1975 Aug, 89(2), 353 - 70
Mutants of Salmonella typhimurium responding to cysteine or methionine: their nature and possible role in the regulation of cysteine biosynthesis; Qureshi MA et al.; Nineteen mutants of Salmonella typhimurium responding to either cysteine or methionine (cym) have been identified amongst cysteine (cys) and methionine (met) auxotrophs . Their growth responses to known intermediates in the related pathways of cysteine and methionine biosynthesis and complementation patterns in abortive transduction tests divided the mutants into six groups . Results of conjugation, cotransduction and deletion mapping experiments substantiated these groups, each of which carried a lesion within known cys genes . Enzyme assays on cym mutants from five of the six groups confirmed their cys gene deficiencies . Growth response and enzyme assay data were not consistent with mutants being leaky cys mutants (spared by methionine) . None of eight cym mutants tested were able to convert {35S}methionine into {35S}cysteine . Selenate specifically inhibits the early enzymes of cysteine synthesis . In cym mutants this inhibition was relieved by cysteine but not by methionine, indicating that cym mutants require active cys enzymes for growth on methionine . There was evidence that methionine stimulated in vivo activity of cys enzymes in a cym mutant . Resistance to inhibition by 1,2,4-triazole results in reduced levels of the O-acetyl serine sulphydrylase . In cym mutants triazole resistance gave unstable suppression of the cym phenotype . Cym mutants may result from mutation in regulatory regions common to each of the cys genes, with the precise role of methionine as yet unknown.

Biochim Biophys Acta, 1975 Jul 27, 397(1), 80 - 93
Anthranilate synthetase-anthranilate 5-phosphoribosylpyrophosphate phosphoribosyl-transferase from Salmonella typhimurium . Inactivation of glutamine-dependent anthranilate synthetase by agarose-bound anthranilate; Grove TH et al.; Exposure of the anthranilate synthetase-anthranilate phosphoribosyltransferase enzyme complex (chorismate pyruvate-lyase (amino-accepting) EC 4.1.3.27 and N-(5-phosphoribosyl)-anthranilate pyrophosphate phosphoribosyl-transferase, EC 2.4.2.18) from Salmonella typhimurium to agarose-bound anthranilate led to the slow inactivation of glutamine-dependent anthranilate synthetase activity, an activity dependent on protein-protein interaction in the enzyme complex . Region I of phosphoribosyltransferase, the location of the enzyme complex glutaminase activity, is the site of alteration . Phosphoribosyltransferase and NH3-dependent anthranilate synthetase activities and trypto phan regulation of phosphoribosyltransferase were unaffected by the anthranilate matrix . The molecular weight (280 000) and subunit molecular weight (62 000) of the enzyme complex eluted from an anthranilate matrix were identical to those of enzyme complex purified by classical methodology . The enzyme complex could be partially protected against inactivation by storiing in 0.1 M L-glutamine or 30% glycerol and completely protected by storing in 50% glycerol at -18 degrees C . Evidence is presented that the anthranilate matrix acts as a hydrophobic matrix and may be binding to and altering a hydrophobic region in the enzyme complex . The anthranilate matrix provides a convenient tool for altering a specific region of an enzyme complex without covalent modification . At the same time, the results demonstrate that affinity matrices are not necessarily innocuous but may subject macromolecules to an adverse environment not previously recognized.

J Biol Chem, 1975 Jul 25, 250(14), 5364 - 9
Inactivation of Salmonella phosphoribosylpyrophosphate synthetase by oxidation of a specific sulfhydryl group with potassium permanganate; Roberts MF et al.; Phosphoribosylpyrophosphate synthetase from Salmonella typhimurium contains four cysteine residues per subunit . Three of these react readily with 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB), forming an active derivative with kinetic and physical properties similar to the native enzyme, but one reacts only under denaturing conditions . Stoichiometric amounts of KMnO4 inactivate the DTNB-treated enzyme . The loss of activity is correlated with the oxidation of the remaining cysteinyl group to cysteic acid by KMnO4 . Amino acid analysis indicates that no other residues are altered . The rate of inactivation of the enzyme is decreased 30-fold by saturatin g concentrations of the substrate ATP . Inorganic phosphate also protects substantially against KMnO4 . Titration of the native enzyme with limiting amounts of KMnO4 shows that the sulfhydryl group essential for activity competes effectively with the other sulfhydryl groups for KMnO4 . These results suggest that the essential sulfhydryl group is near the active site, and that KMnO4, a phosphate analogue, can act as an active site-directed reagent at the ATP binding site of the enzyme . The KMnO4-oxidized enzyme is more highly aggregated than untreated enzyme and fails to bind ATP appreciably.

Experientia, 1975 Jul 15, 31(7), 787 - 8
Effect of excision repair system on antibacterial and mutagenic activity of daunomycin and other intercalating agents in Salmonella typhimurium; Pani B et al.; Daunomycin and adriamycin, are more mutagenic and antibacterial for a strain of Salmonella typhimurium defective for the uvrB gene than for its uvr+ counterpart . Other intercalating agents, as some acridine dyes, affect equally the two bacterial strains.

J Biol Chem, 1975 Jul 10, 250(13), 5089 - 96
A transport system for phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate in Salmonella typhimurium; Saier MH Jr et al.; Salmonella typhimurium strain LT-2 was found to utilize phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate as sole sources of carbon and energy for growth, but Escherichia coli strains did not . The following evidence suggests that this growth difference was due to the presence in Salmonella cells of an inducible phosphoglycerate permease distinct from previously studied transport systems: (a) The ability of cells to take up 3-phospho{14-C}glycerate was induced by growth in the presence of phosphoenolpyruvate, 2-phosphoglycerate, or 3-phosphoglycerate, but not glycerate, alpha-glycerophosphate, or other carbon sources tested . (b) Uptake of 3-phospho{14-C}glycerate was strongly inhibited by the three nonradioactive inducers of 3-phosphoglycerate uptake, but not by glycerate or alpha-glycerophosphate . (c) Mutants which lost the ability to utilize and take up 3-phosphoglycerate simultaneously lost the ability to utilize 2-phosphoglycerate and phosphoenolpyruvate, but not other compounds tested . (d) Mutant strains which constitutively synthesized the phosphoglycerate transport system could use both phosphoglycerates and phosphoenolpyruvate as sole sources of phosphate at low substrate concentrations . (e) A strain lacking alkaline and acid phosphatases could still grow with 3-phosphoglycerate as sole carbon source . Maximal rates of 3-phospho{14-C}glycerate uptake occurred at pH 6 in the presence of an exogenous energy source . The apparent Km for 3-phosphoglycerate uptake under these conditions was about 10-minus 4 M . The maximal uptake rate (but not the Km) was dependent on potassium ions . Although synthesis of the phosphoglycerate transport system appeared to be under adenosine 3:5-monophosphate control, glucose repressed induction only slightly . The genes controlling synthesis of the phosphoglycerate transport system (pgt genes) appeared to map at about 74 min on the Salmonella chromosome.

Am J Vet Res, 1975 Jul, 36(7), 1015 - 9
Endotoxin from Fusobacterium necrophorum of bovine hepatic abscess origin; Warner JF et al.; The endotoxic activity of Fusobacterium necrophorum bov 5 was investigated . The supernatant (S) fluid and cell wall (CW) preparation, obtained after differential centrifugation of the ruptured cell mass, were lethal for mice . The toxicity of the S fluid was stable during prolonged storage, treatment with formalin, and heating for 15 minutes at 80, 100, and 121 C, but was destroyed by alkaline hydrolysis with 0.25 N NaOH . The toxic factor was found in a high molecular weight (MW) fraction after gel filtration . The properties exhibited by the toxic S fluid resembled those of endotoxic lipopolysaccharide (LPS) . Extracted and partially purified LPS (endotoxin) from F necrophorum bov 5 demonstrated a mouse median lethal dose (mouse LD50) of 16.8 mg/kg of body weight . The toxic LPS material, a high molecular weight moiety as estimated by gel filtration, was resistant to ribonuclease (RNase), deoxyribonuclease (DNase), and pronase treatment . A positive Shwartzman reaction (median skin lesion dose (SLD50) equal to 3.32 mug/kg of body weight) and biphasic fever response (minimal dose required to produce a fever index of 40 sq cm which falls on the linear portion of dose-response curve (FL40) equal to 0.41 mug/kg of body weight) further indicated the toxin was endotoxin in nature . The LPS from F necrophorum bov 5 was less toxic than Salmonella typhimurium LPS; but had considerable toxicity for experimental animals . The toxic activity of the partially purified F necrophorum bov 5 endotoxin was separated into 2 fraction regions by diethylaminoethyl (DEAE)-cellulose chromatography . The data provide evidence for the production of a potent endotoxin, possibly composed of more than one toxic component, which may be released upon cell disruption.

Nucleic Acids Res, 1975 Jul, 2(7), 1143 - 51
The metabolism of N4-hydroxycytidine-a mutagen for Salmonella typhimurium; Popowska E et al.; Salmonella typhimurium cells were grown in the presence of (14C)-N4-hydroxycytidine (N4OHcyd), a mutagenic nucleoside, and labelling in DNA and RNA digest was traced . The results show that this analogue is incorporated into RNA at a level of 40 mug/100 mg, and into DNA with a yield at least 100 times smaller . Some N-minus4OHcyd was rapidly metabolized and labelling was found in all ribo- and deoxyribo-nucleosides.

J Gen Microbiol, 1975 Jul, 89(1), 133 - 6
Sex pili as immunogens; Smith HW et al.; Groups of chickens were vaccinated intravenously with live cultures of Escherichia coli K12 possessing transfer factors F, I, A2 or no transfer factor (Tra-minus) and their immunity challenged by injecting them intravenously with an F-plus strain of Salmonella heidelberg or an F-plus or I-plus strain of Salmonella typhimurium . Compared with the Tra-minus strain, vaccination with the F-plus, but not the I-plus or A2-plus, K12 strain significantly reduced the mortality rate caused by the F-plus salmonella strains; vaccination with the I-plus or A2-plus, but not the F-plus, K12 strain significantly reduced the mortality rate caused by the I-plus salmonella strain.

Can J Microbiol, 1975 Jul, 21(7), 1132 - 6
Cell surface protein of Salmonella typhimurium; Kabir S; Lactoperoxidase-catalyzed radioiodination with Na125I was performed both on intact Salmonella typhimurium 1195 and on ghost membrane isolated from the same bacterial strain . Ghost membrane was also prepared from radioiodinated whole bacteria . The labelled proteins from both these ghost membrane preparations were compared by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate to identify the cell surface proteinmfrom the results obtained it was concluded that one major protein with an apparent molecular weight of 1200-1300 was exposed on the exterior surface of the ghost membrane.

J Bacteriol, 1975 Jul, 123(1), 233 - 41
Properties of the imidazolylacetolphosphate aminotransferase produced in a mutant demonstrating no apparent genetic involvement of the structural gene; Roberts JH et al.; Genetic studies with strain hisBH22 of Salmonella typhimurium indicate it contains a deletion within the histidine operon involving part of the hisH gene and all of the hisB gene, but not extending into the adjacent hisC gene which is adjacent to hisB . However, the specific activity of the hisC product, imidazolylacetolphosphate aminotransferase (EC 2.6.1.9), in this strain is only 10 to 15% of that found in extracts from other mutants with a normal hisC gene . We have examined the rate of aminotransferase synthesis in this mutant and we find that the rate of synthesis of aminotransferase activity is low in mutant hisBH22, but the rate increases as the temperature of growth is lowered from 37 to 23 C . The low rate of enzyme accumulation is not due to holoenzyme instability at 37 C but instead is due to apoenzyme instability at this temperature . By transducing the hisBH22 marker into a pyridoxine auxotroph and derepressing the histidine operon under conditions where the intracellular concentration of pyridoxal phosphate would be expected to be low, we were able to demonstrate significant apoenzyme production only at the lower temperature . We suggest that the explanation for low aminotransferase specific activity at 37 C is due to the presence of reduced numbers of catalytically active units caused by normal production of an unstable mutant apoenzyme with only approximately 15% of the molecules being activated to holoenzyme . The holoenzyme from strain hisBH22 is stable during growth of this strain at 37 C.

J Bacteriol, 1975 Jul, 123(1), 1 - 6
Conservation of Salmonella typhimurium deoxyribonucleic acid by chromosomal insertion in a partially diploid Escherichia coli hybrid; Johnson EM et al.; A partially diploid Escherichia coli hybrid recovered from mating with a Salmonella typhimurium donor was converted to an Hfr strain, designated WR2080, as a means to examine the manner in which the added Salmonella genetic material was conserved in it . The Salmonella argH-+, metB-+, and RHA-+ alleles contained as supernumerary genes in WR2080 were transferred together to E . coli recipients in interrupted mating experiments approximately 25 min after initial parental contact; transfer of the allelic E . coli genes by a haploid Hfr of the same transfer orientation occurred between 23.5 min (argH-+) and 25 min (rha-+) after initial contact . Entry of the E . coli ilv-+ marker of WR2080 in these experiments occurred at 29.5 min, 1.5 min later than the entry time of this marker from the haploid E . coli Hfr . When unselected inheritance of the recessive E . coli argH-minus and rha-minus alleles of WR2080 was examined among ilv-+ selected E . coli recipients in which unselected inheritance of the Salmonella donor genes was shown to be low (8%), inheritance of argH-minus was only 7%, whereas 51% inherited the neighboring rha-minus gene . In a comparative cross employing a haploid E . coli Hfr, in which rha inheritance was similar at 56%, argH inheritance was 41% . It was concluded that the Salmonella genes contained in WR2080 were conserved on a genetic segment about 1.5 min in length chromosomally inserted near the allelic E . coli genes, thus creating a duplication on that region within the hybrid chromosome.

J Virol, 1975 Jul, 16(1), 101 - 6
Transport in bacteriophage P22-infected Salmonella typhimurium; Khandekar PS et al.; There was rapid efflux of L-leucine, L-phenylalanine, and alpha-methyl-D-glucoside after infection of Salmonella typhimurium with the clear plaque mutant C1 of phage P22 . The efflux was similar to that observed with cyanide or arsenate treatment except that there was partial recovery in the case of phage infection and almost complete recovery under the condition of lysogeny . There was no efflux after infection with the temperature-sensitive mutant ts16C1 at nonpermissive temperature . Superinfection of superinfection exclusion negative lysogen (sie A minus sie B minus) with C1 led to efflux, whereas the efflux was much less on superinfection of sie A+ Sie B+ lysogen . These results indicate that an effective injection process is enough to cause depression in the cellular transport processes.

Cancer Res, 1975 Jul, 35(7), 1813 - 8
Dietary modifications affecting the mutagenicity of N-nitroso compounds in the host-mediated assay; Zeiger E; The effects of various dietary modifications on the mutagenicity of dimethylnitrosamine (DMNA), N-nitrosomorpholine, and N-methyl-N-nitrosourea for Salmonella typhimurium his G-46 in the host-mediated assay were studied . The diets used were:chow, complete semisynthetic, protein-free, and all-casein, in addition to a 24-hr starvation regimen . The mutagenicity of DMNA and N-nitrosomorpholine, which require metabolic activation for their biological activity, was depressed by the complete semisynthetic diet, as compared to the mutagenicity in mice fed the chow diet . DMNA mutagenicity was depressed by the protein-free diet and enhanced by pure casein as compared with the complete semisynthetic diet . N-Nitrosomorpholine mutagenicity was enhanced by starvation, but results with mice fed the protein-free and all-casein diets were ambiguous . N-Methyl-N-nitrosourea, which does not require metabolic activation for its biological activities, responded in an opposite manner to that of DMNA; its mutagenicity was enhanced by the complete semisynthetic and protein-free diets, but was depressed by the all-casein diet.

Biochem J, 1975 Jul, 150(1), 21 - 9
Salmonella typhimurium HfrA, a mutant in which adenosine triphosphate can drive amino acid transport but not energy-dependent nicotinamide nucleotide transhydrogenation; Kay WW et al.; In contrast with wild-type Salmonella typhimurium LT2, strain HfrA did not have ATP-driven energy-dependent transhydrogenase activity, although ATP-dependent quenching of atebrin fluorescence was normal . Respiration-dependent and energy-independent transhydrogenase, and Ca2+-activated ATPase (adenosine triphosphatase) activities were similar in both strains . Purified ATPases from the two strains had similar specific activities, similar subunit polypeptides, and were equally effective in restoring energy-dependent transhydrogenase activities to membrane particles of strain LT2 from which the ATPase had been stripped . The purified ATPases from both strains could restore respiration-dependent but not ATP-dependent transhydrogenation to stripped particles of strain HfrA . Both strains grew aerobically equally well on salts media containing glucose, malate, succinate, citrate, acetate, pyruvate, fumarate, lactate or aspartate as substrates . Growth on glucose under anaerobic conditions was similar . Strains LT2 and HfrA were equally effective in the accumulation under both aerobic and anaerobic conditions of the amino acids proline, phenylalanine, histidine, lysine, isoleucine and aspartic acid . Inhibition of amino acid accumulation by KCN and dicyclohexylcarbodi-imide occurred to the same extent in both strains . The complete inhibition by dicyclohexylcarbodi-imide of amino acid uptake under anaerobic conditions suggested that ATP could drive amino acid uptake in both strains . The ability of strain HfrA to carry out ATP-dependent transport or quenching of atebrin fluorescence but not ATP-dependent transhydrogenation is different from the wild-type strain and from any previously described energy-coupling mutant . It is difficult to reconcile the properties of this mutant with the chemiosmotic hypothesis.

Boll Ist Sieroter Milan, 1975 Jun 26, 54(2), 105 - 7
Mutagenic activity of anthraquinone derivatives used as dyes in a textile factory; Tamaro M et al.; Some anthraquinone derivatives used as dyes in a textile factory have been tested for their mutagenic activity on the Ames' strains of Salmonella typhimurium . 1-amino-4-hydroxy-anthraquinone proved to be a mutagen of the frameshift type . It is active without need of metabolic activation . Studies are in progress in order to clarify if the mutagenic activity of other substituted anthraquinones, which do not act as direct mutagens, can become evident after metabolic activation . Further tests are needed to decide if substituted anthraquinones are hazardous for exposed people.

J Biol Chem, 1975 Jun 25, 250(12), 4410 - 7
Carbamylphosphate synthetase from Salmonella typhimurium . Regulations, subunit composition, and function of the subunits; Abdelal AT et al.; Carbamylphosphate synthetase was purified to homogeneity from a derepressed strain of Salmonella typhimurium by a procedure based on affinity chromatography employing immobilized glutamine . The enzyme catalyzes the synthesis of carbamylphosphate from either ammonia or glutamine together with ATP and bicarbonate . The ATP saturation curve of either nitrogen donor is sigmoidal (n equals 1.5) but the affinity for ATP is higher with ammonia . In addition to the feedback inhibition by UMP and activation by ornithine which we previously reported (1), the activity was found to be stimulated by IMP and phosphoribosyl-1-pyrophosphate . Evidence from pool measurements in enteric bacteria by others suggests that of the latter two compounds only phosphoribosyl-1-pyrophosphate is physiologically significant . All effectors regulate enzyme activity by altering its affinity for ATP . Glutamine also modulates the affinity for ATP; it is increased as glutamine concentratiions decrease, an effect that could serve to insulate the cell against major changes in carbamylphosphate synthesis in response to fluctuations in concentration of glutamine . The molecular weight of the holoenzyme was estimated to be 150,000 by sucrose density gradient centrifugation in triethanolamine and Tris-acetate buffers in which the enzyme is a monomer . In the presence of ornithine in potassium phosphate buffer, the enzyme is an oligomer with a molecular weight of 580,000 . This transition has been exploited as an alternate route of purifying the enzyme to homogeneity using successive sucrose density centrifugation . Polyacrylamide gel electrophoresis of the enzyme in the presence of sodium dodecyl sulfate shows that the enzyme consists of two unequal subunits with molecular weights of 110,000 and 45,000 . The two subunits were separated by gel filtration in the presence of 1 M potassium thiocyanate, ATP, MgCl2, glutamine, NH4Cl, ornithine, and UMP . The heavy subunit catalyzes the synthesis of carbamylphosphate from ammonia but not glutamine . The ATP saturation curve for the separated heavy subunit is still sigmoidal (n equals 1.4 and So.5 equals 0.3 mM) . The ammonia dependent activity of the heavy subunit is stimulated by the activators ornithine, IMP, and phosphoribosyl-1-pyrophosphate but is only marginally inhibited by high concentrations of UMP . The addition of the light subunit restored full ability to utilize glutamine as well as normal sensitivity to UMP . Purified subunits were used for in vitro complementation studies with strains carrying mutations in pyrA, the structural gene encoding carbamylphosphate synthetase . The results indicate that the pyrA region encodes both subunits and that the structural genes for the two polypeptides are linked . A deletion mutant lacking both subunits of carbamylphosphate synthetase also lacked any ability to synthetize carbamylphosphate from ammonia . Hence, unlike certain other bacteria, S . typhimurium does not possess a carbamate kinase.

Am J Epidemiol, 1975 Jun, 101(6), 502 - 11
The Middleton outbreak: 125 cases of foodborne salmonellosis resulting from cross-contaminated food items served at a picnic and a smorgasbord; Levy BS et al.; One hundred and twenty-five of 173 people who ate at a picnic and/or a smorgasbord prepared by a bar-restaurant in a Midwestern town in September 1973 developed diarrhea, abdominal cramps, and other symptoms 23 hours (median time) later . Eleven were hospitalized . Stool cultures from 18 ill individuals grew Salmonella infantis, Salmonella agona, and Salmonella schwarzengrund . Stool cultures from 5 of 8 restaurant employees grew S . infantis or S . agona . Cultures of remaining foods and food-contact surfaces were negative . Food-specific attack rates, based on interviews with 121 eaters, implicated potato salad and chicken dressing as vehicles of transmission, both likely contaminated when prepared in pans that shortly before contained uncooked, chicken pieces suspected to have harbored salmonellae . Chickens were eventually traced to 3 farms where feed samples were found to contain Salmonella typhimurium and Salmonella cubana, raising the possibility that other feed samples may have contained the serotypes responsible for the outbreak . The main control measure was temporarily closing the food service, which was to have catered a large church picnic the next day . The outbreak had an economic impact estimated at $28,733.

Br J Exp Pathol, 1975 Jun, 56(3), 231 - 43
Cellular and humoral aspects of host resistance in murine salmonellosis; Marecki NM et al.; Mice were challenged with a highly virulent strain of Salmonella typhimurium by intraperitoneal injections . At relatively low infecting doses, immunizations with either viable attenuated or heat killed Salm . typhimurium were found to be equally protective against otherwise fatal infections . Pre-opsonization of virulent salmonellae significantly increased the survival rate of mice infected with small numbers of the pathogen . By a cell culture method, peritoneal macrophages of mice were shown to be innately capable of destroying the ingested virulent Salm . typhimurium . Macrophages from previously infected mice did not appear to have any significant increase in their bactericidal activity against salmonellae, but they possessed cytophilic antibodies specific against the H and the O antigens of Salm . typhimurium . It is believed that humoral elements play an important role in acquired immunity in murine salmonellosis by opsonization of the pathogen.

J Bacteriol, 1975 Jun, 122(3), 994 - 1000
Separate regulation of transport and biosynthesis of leucine, isoleucine, and valine in bacteria; Quay SC et al.; Since both transport activity and the leucine biosynthetic enzymes are repressed by growth on leucine, the regulation of leucine, isoleucine, and valine biosynthetic enzymes was examined in Escherichia coli K-12 strain EO312, a constitutively derepressed branched-chain amino acid transport mutant, to determine if the transport derepression affected the biosynthetic enzymes . Neither the iluB gene product, acetohydroxy acid synthetase (acetolactate synthetase, EC 4.1.3.18), NOR THE LEUB gene product, 3-isopropylmalate dehydrogenase (2-hydroxy-4-methyl-3-carboxyvalerate-nicotinamide adenine dinucleotide oxido-reductase, EC 1.1.1.85), were significantly affected in their level of derepression or repression compared to the parental strain . A number of strains with alterations in the regulation of the branched-chain amino acid biosynthetic enzymes were examined for the regulation of the shock-sensitive transport system for these amino acids (LIV-I) . When transport activity was examined in strains with mutations leading to derepression of the iluB, iluADE, and leuABCD gene clusters, the regulation of the LIV-I transport system was found to be normal . The regulation of transport in an E . coli strain B/r with a deletion of the entire leucine biosynthetic operon was normal, indicating none of the gene products of this operon are required for regulation of transport . Salmonella typhimurium LT2 strain leu-500, a single-site mutation affecting both promotor-like and operator-like function of the leuABCD gene cluster, also had normal regulation of the LIV-I transport system . All of the strains contained leucine-specific transport activity, which was also repressed by growth in media containing leucine, isoleucine and valine . The concentrated shock fluids from these strains grown in minimal medium or with excess leucine, isoleucine, and valine were examined for proteins with leucine-binding activity, and the levels of these proteins were found to be regulated normally . It appears that the branched-chain amino acid transport systems and biosynthetic enzymes in E . coli strains K-12 and B/r and in S . typhimurium strain LT2 are not regulated together by a cis-dominate type of mechanism, although both systems may have components in common.

Am J Vet Res, 1975 Jun, 36(6), 839 - 41
Enzootic occurrence of chloramphenicol-resistant Salmonella typhimurium var copenhagen in calf population; Sato G et al.; Chloramphenicol (CP)-resistant Salmonella typhimurium var copenhagen was frequently isolated (44.1 to 76.7%) from dead, diseased, and healthy calves on 3 farms in 1973 in northern Japan . On 2 of the farms, CP-resistant salmonella appeared suddenly during an epizootic of salmonella infection, and persisted . Of 87 CP-resistant to tetracycline (TC), streptomycin (SM), and sulfonamides (SA), and the remaining 13 isolates from dead calves on a farm were resistant to TC, SM, SA, and kanamycin (KM) . Resistance patterns of all CP-resistant isolates were transferred completely.

Genetics, 1975 Jun, 80(2), 227 - 37
Selection for a large genetic duplication in Salmonella typhimurium; Straus DS; Salmonella typhimurium strains containing a duplication of nearly a third of the genome have been isolated by a simple procedure involving selection for improved utilization of L-malate as sole carbon source . The duplication occurs at a very high spontaneous frequency . Strains containing the duplication can be isolated selectively on malate medium, or by a non-selective procedure involving Hfr conjugation . When strains containing the duplication are maintained on non-selective medium, the duplication is readily lost . Genetic evidence suggests that the duplication is chromosomal and tandem . The fact that the recA gene is included in the duplication has been used to obtain evidence that the recA1 marker is recessive to its wild-type allele . Unlike tandem duplications previously described in I . coli, the duplication described in this report appears to have unique endpoints.

Mutat Res, 1975 Jun, 28(3), 405 - 20
Mutagenicity of organophosphorus compounds in bacteria and Drosophila; Hanna PJ et al.; 140 Organophosphorus compounds (OP's) have been tested for mutagenic activity in bacteria, principally by using two specially constructed sets of tester strains of the bacteria Salmonella typhimurium and Escherichia coli . It was found that 20% gave positive mutagenic responses and that this group of chemicals produce base subsitutions rather than frame-shift mutations . In most cases the DNA repair genes exrA+ and recA+ were required for mutagenic activity . Seven compounds were further tested in Drosophila melanogaster for the ability to induce recessive lethal mutations . In some of these cases the doses administered to the flies had to be very low due to the highly toxic nature of the compounds . To over-come this problem, the accumulation of recessive lethal mutations was measured in populations which were continually exposed to the compounds over a period of some 18 months . During this time the populations developed increased resistance to the compound and so the dose administered could gradually be increased . Six of the compounds were mutagenic . Of the compounds tested in both systems, those showing mutagenic activity in bacteria were also mutagenic in Drosophila, those not mutagenic in bacteria were not mutagenic in Drosophila.

J Immunol, 1975 Jun, 114(6), 1720 - 5
Effect of nonspecific stimulation on the defense mechanisms of inbred mice; Medina S et al.; Acquired resistance to facultative intracellular parasites was investigated in C57BL/6J inbred mice susceptibe to Salmonella typhimurium but inherently resistant to Listeria monocytogenes and in A/J inbred mice which showed the reverse relationship . A/J but not C57BL/6J mice were protected against S . typhimurium challenge by S . typhimurium phenol vaccine, S . typhimurium purified RNA, or L . monocytogenes purified RNA . C57BL/6J but not A/J could be protected against L . monocytogenes challenge by L . monocytogenes phenol vaccine, S . typhimurium RNA, or L . monocytogenes RNA . Yeast RNA, calf thymus RNA, BCG and poly (I:C) protected A/J against Salmonella and C57BL/6J against Listeria challenge . Enumeration of viable organisms in the RNA and BCG-stimulated animals after challenge indicated that macrophage activation had probably taken place . The RNA-elicited protection was long lasting and waned after about 60 days . Enhanced resistance to S . typhimurium and L . monocytogenes can be stimulated by nonliving substances bearing no known antigenic relationship to the pathogen . Enhanced resistance is elicited only in the host with a background of inherent resistance to the specific pathogen.

J Bacteriol, 1975 Jun, 122(3), 1025 - 31
Gene order of the histidine utilization (hut) operons in Klebsiella aerogenes; Goldberg RB et al.; P1-sensitive mutants of Klebsiella aerogenes were isolated and the gene order of the hut region was then determined using P1-mediated transduction . The genes are located in the Klebsiella chromosome between gal and bio as in Salmonella typhimurium . The gene order, gal, hutI, hutG, hutC, huU, hutH, bio is also the same as that observed in S . typhimurium.

J Bacteriol, 1975 Jun, 122(3), 1006 - 16
Mutations affecting glutamine synthetase activity in Salmonella typhimurium; Kustu SG et al.; A positive selection procedure has been devised for isolating mutant strains of Salmonella typhimurium with altered glutamine synthetase activity . Mutants are derived from a histidine auxotroph by selecting for ability to grow on D-histidine as the sole histidine source . We hypothesize that the phenotype may be based on a regulatory increase in the activities of the D-histidine racemizing enzymes, but this has not been established . Spontaneous glutamine-requiring mutants isolated by the above selection procedure have two types of alterations in glutamine synthetase activity . Some have less than 10% of parent activity . Others have significant glutamine synthetase activity, but the enzyme have an altered response to divalent cations . Activity in mutants of the second type mimics that of highly adenylylated wild-type enzyme, which is believed to be in-active in vivo . Glutamine synthetase from one such mutant is more heat labile than wild-type enzyme, indicating that it is structurally altered . Mutations in all strains are probably in the glutamine synthetase structural gene (glnA) . They are closely linked on the Salmonella chromosome and lie at about min 125 . The mutants have normal glutamate dehydrogenase activity.

J Bacteriol, 1975 Jun, 122(3), 1081 - 90
Cyclic 3', 5'-adenosine monophosphate phosphodiesterase mutants of Salmonella typhimurium; Alper MD et al.; Positive selection procedures for mutants of Salmonella typhimurium lacking cyclic 3', 5'7-adenosine monophosphate (cAMP) phosphodiesterase have been devised . The gene (cpd) coding for this enzyme has been located on the chromosome and shown to be 25% co-transducible with metC using phage P22 . The mutants have been used to investigate the role of the enzyme in the control of genes whose expression is known to be dependent on cAMP . Significant alterations in the regulation of some but not others of these genes have been observed in these mutants . Mutants lacking the cAMP phosphodiesterase are more sensitive than their parents to a variety of antibiotics that appear to enter the cell through cAMP-dependent transport systems . They grow faster than the wild type on succinate-ammonia-salts, and glucose-proline-salts media and are inhibited by added cAMP on glucose, citrate, or glycerol-ammonia salts media whereas the wild type is unaffected . Neither the growth of Salmonella typhimurium on glycerol or citrate media nor the level of acid hexose phosphatase in the strain is affected by the loss of cAMP phosphodiesterase . In addition, the mutant strains are extremely sensitive to high levels of cAMP . Loss of the cAMP phosphodiesterase in strains unable to synthesize cAMP (adenyl cyclase negative) reduces by 10-fold the requirement for exogenous cAMP for expression of catabolite-sensitive phenotypes . These results suggest that through its control of cAMP levels in the cell the phosphodiesterase may be involved in the regulation of certain classes of catabolite-sensitive operaons and also in protecting the cell against high levels of cAMP.

Zh Mikrobiol Epidemiol Immunobiol, 1975 May, (5), 25 - 9
{Study of the sensitivity of a morphological mutant of S . typhimurium to irradiation}; Sakanian VA et al.; Morphological Salmonella typhimurium LT2 WT--ED 143 mutant was similar by the character of the UV-sensitivity to the lon-mutants of Escherichia coli K-12 . The paper treats of the data on the UV-sensitivity of the mutant and the initial strains at various growth phases, by the capacity to restore the irradiated P22 and Felix O bacteriophages and by the effect of various postradiational treatment on the irradiated strains . Data are presented on densitometry of the membrane proteins of the initial and the mutant strains, permitting to associate the unusual morphology, disturbed division and increased UV-sensitivity with the state of the membrane components of the bacterial cell.

Poult Sci, 1975 May, 54(3), 848 - 55
Hemagglutinating properties of Salmonella typhimurium strains isolated from avian sources; Williams JE et al.; A total of 565 strains of Salmonella typhimurium and S . typhimurium var . copenhagen, isolated from avian species, were examined for their ability to cause hemagglutination of turkey erythrocytes . Results showed that 541 (95.7%) of the strains caused varying degrees of hemagglutination . The hemagglutinating principle was maintained in cultures stored at 5 degrees C . as formalized suspensions for as long as 6 months . It was destroyed by exposure to a temperature of 80 degrees C . for 1 minute or to absolute ethyl alcohol at 37 degrees C . for 24 hours . The hemagglutinating principle was best preserved in cultures by infrequent transfers, growth in liquid media, lyophilization or storage at low temperatures . Addition of d-mannose to bacteria-erythrocyte mixtures at a final concentration of 0.5% completely inhibited the hemagglutinating activity of the cultures . A concentration of 1% d-mannose added to crystal-violet-stained antigen preparations of S . typhimurium eliminated entirely the hemagglutinating effect of positive cultures and did not interfere with regular agglutination reactions . The hemagglutinating activity of S . typhimurium strains is apparently due to the presence of rigid appendage (fimgriae) on the surface of the bacterial cells . Results from these studies showed that fimbriated cultures are quite common among strains of S . typhimurium.

J Infect Dis, 1975 May, 131(5), 553 - 8
Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine; Germanier R et al.; A gal E mutant of Salmonella typhi was isolated; results obtained with Salmonella typhimurium and the mouse as a model for human typhoid fever indicated that this mutant has the potential for use as a live, oral typhoid vaccine . The mutant, Ty 21a, took up galactose from exogenous sources and accumulated sufficient quantities of galactose-1-phosphate and uridine diphosphate galactose to cause lysis of the cells, an event that resulted in the avirulence of the strain . Galactose was incorporated sufficiently into the cell wall of Ty 21a to allow the synthesis of smooth-type lipopolysaccharides, which are necessary for the proper immunogenicity . Cells of strain Ty 21a, when given intraperitoneally, protected mice against lethal challenge with strain Ty 2 of S . typhi.

J Bacteriol, 1975 May, 122(2), 549 - 56
Hycanthone and its congeners as bacterial mutagens; Cook TM et al.; Hycanthone methanesulfonate (HCT) was shown to induce "forward" and "reverse" mutations in Salmonella typhimurium and Escherichia coli . Mutational effects of HCT on S . tyhhimurium TA1532 were concentration and time dependent . A comparison of mutagenic potency for TA1532 was made between HCT and the frame-shift mutagens quinacrine and ICR-191 . An investigation of structure-activity relationships revealed the substituent in the 4-position of ring A to be critical for mutagenicity . Activity was found when this group was a hydroxymethyl (i.e., HCT) or an aldehyde (Win 25,315), but the analogues having a carboxyl group (Win 25,850) or methyl group (lucanthone) in this positionwere inactive . Removal of a single ethyl group from the side chain did not affect mutagenic activity inasmuch as the potency of desethyl HCT (Win 27,262) equaled that of HCT on a molar basis . A marginal activity was found with a sample of HCT sulfoxide (win 27,266), but this sample was found to contain traces of HCT . The HCT analogue with a terminal N-oxide in the side chain (Win 29,329) was inactive at the concentration tested.

Infect Immun, 1975 May, 11(5), 944 - 8
Interaction of complement components with a serum-resistant strain of Salmonella typhimurium; Reynolds BL et al.; Salmonella typhimurium C5 is under normal conditions (physiological saline containing 0.002 M Mg2+) resistant to the action of antibody and complement (C) . It becomes sensitive, however, when suspended in tris(hydroxymethyl)-aminomethane buffer (Reynolds and Pruul, 1971; Reynolds and Rowley, 1969) . The interaction of complement components with this strain sensitized with specific antibody has been studied to identify the intermediate step at which inhibition occurs . The components C1 yields C2 react normally, as has been shown by lysis of complement-treated cells incubated with complement in ethylenediaminetetraacetic acid . Also, the reaction of C3 can be demonstrated by positive immune adherence and agglutination with anti-C3 . The complement-treated cells do not, however, react with rabbit C6 to 9 or rabbit serum lacking C6 in tris(hydroxymethyl)aminomethan buffer . We conclude from these date that C5 can not react effectively under normal conditions . In contrast, if bacteria-antibody complexes are pretreated with rabbit serum lacking C6 in tris(hydroxymethyl)aminomethane buffer, they are readily lysed by incubation with C6 to 9 . Thus, C5 can react with the bacterial surface in tris(hydroxymethyl)-aminomethane buffer.

Clin Chem, 1975 Apr, 21(4), 528 - 32
Serum zinc, iron, and copper concentrations during typhoid fever in man: effect of chloramphenicol therapy; Pekarek RS et al.; In volunteers experimentally infected with Salmonella typhi, serum iron and zinc concentrations became significantly depressed and there was a concomitant rise in serum copper before the onset of overt clinical illness . However, after several days of fever and the initiation of chloramphenicol therapy, serum iron and zinc concentrations significantly increased . Additional studies--in volunteers with typhoid fever treated with chloramphenicol, in a volunteer with typhoid fever receiving cefazolin and gentamicin, and in untreated rhesus monkeys infected with Salmonella typhimurium--provided evidence that the increase in serum iron concentration during the febrile phase was the result of chloramphenicol therapy, whereas the increase in serum zinc concentrations was a disease-related phenomenon . The importance of trace-metal monitoring during infectious disease and chemotherapy is discussed.

J Biol Chem, 1975 Apr 10, 250(7), 2574 - 80
Purification and properties of a periplasmic glutamate-aspartate binding protein from Escherichia coli K12 strain W3092; Willis RC et al.; A protein which binds both glutamate (K-D = 0.8 muM) and aspartate (K-D = 1.2 muM) has been purified to homogeneity (290-fold) from the periplasmic fraction released from Escherichia coli W3092 by the cold osmotic shock procedure . The apparent molecular weight of the glutamate-aspartate binding protein is approximately 31,000 as judged by gel electrophoresis, gel filtration, and sedimentation equilibrium centrifugation; and the protein has a pI of 9.69 . This protein contains 2 half-cystine residues and is dependent on a dithiothreitol-sensitive component for renaturation to an active conformation following urea or guanidine treatment . Of the natural amino acids only the L isomers of glutamate, aspartate, glutamine, asparagine, and alanine were inhibitors of either {C}glutamate or {14C}aspartate binding and the inhibitions were competitive . Only one binding site is indicated per molecule of protein . Antibody prepared against the glutamate-asparate binding protein does not cross-react with purified glutamine binding protein or any other component of osmotic shock fluid . The antibody does cross-react with osmotic shock fluids obtained from E . coli strains B and W and Salmonella typhimurium OT2 . The glutamate-aspartate binding protein-antibody complex does not bind either glutamate or aspartate . The protein may be similar to the glutamate binding activity detected in the periplasmic fraction released from E . coli strain B (Miner, K.M., and Frank, L . (1974) J . Bacteriol . 117, 1093-1098) and strain K12 CS (Barash, H., and Halpern, Y.S . (1971) Biochem . Biophys . Res . Commun . 45, 681-688) . This protein appears to function in the transport of glutamate by E . coli strain W cultured in minimal medium with succinate as the carbon source (Willis, R.C., and Furlong, C.E . (1975) J . Biol . Chem . 250, 2581-2586.

Am J Physiol, 1975 Apr, 228(4), 1183 - 7
Alterations in hepatic chromatin template availability during infection; Earp HS; Hepatic chromatin was isolated from rats at various times after inoculation with either live or heat-killed bacteria . The chromatin was assayed under conditions that allow determination of the DNA template available to support in vitro transcription . Both a fulminant Diplococcus pneumoniae and a milder Salmonella typhimurium infection produced time-related increases in hepatic chromatin template availability when compared to chromatin isolated from rats inoculated with heat-killed bacteria . Both timing and magnitude of increased template availability correlated with the severity of the infection . The earliest change observed was a 50 percent rise in availability noted 4 h after inoculation with D . pneumoniae . This preceded the onset of fever, as well as other known heaptic consequences of systemic infection . After 24 h of infection the maximum rise of 90 percent occurred . Similar changes developed during S . typhimurium infection, but were slower in onset and smaller in magnitude . Adrenalectomy prior to infection enhanced the severity of the disease but markedly blunted the increase in template availability . The data are consistent with the hypothesis that systemic infection regulates the hepatic metabolic response to infection through transcriptional control and that a permissive or stimulatory action of glucocorticoids is involved in the increases in template availability effected.

Avian Dis, 1975 Apr-Jun, 19(2), 342 - 52
Influence of rofenaid-40 feed medication on an experimental Salmonella infection in chickens; Maestrone G et al.; Rofenaid-40 administered at 0.02% in feed to chickens experimentally infected with Salmonella typhimurium resulted in less colonization and shedding of S . typhimurium than in unmedicated chickens . The antibacterial sensitivity pattern of S . typhimurium isolated from infected birds had not changed after exposure to Rofenaid for 56 days.

Mutat Res, 1975 Apr, 28(1), 27 - 30
Mutagenicity testing with Salmonella typhimurium strains . I . Unusual phenotypes of the tester strains; Speck WT et al.; Some of the Salmonella typhimurium strains in mutagenesis testing are atypical . Unlike the wild S . typhimurium these do not produce H-2-S, are not agglutinated by S . typhimurium typing sera and on fermentation of carbohydrates they do not produce gas . Thus these tester strains cannot readily be identified as S . typhimurium by standard laboratory procedures . This may cause a problem in the differentiation of tester strains from bacterial contaminants . The possibility exits that these phenotypic traits may affect the response of the strains to mutagens.

Int J Radiat Biol Relat Stud Phys Chem Med, 1975 Apr, 27(4), 371 - 5
{Mutagenicity testing of irradiated laboratory animal feed in the 'host-mediated' assay with Salmonella typhimurium G 46}; Munzner R et al.; Food irradiated with 10 MeV-electrons (dose: 4-5 Mrad) was tested for mutagenic effects, using the host-mediated assay . Irradiated 'Altomin' (a pelleted laboratory diet) was fed to mice for 9 to 44 days . After the 30th day of feeding, the animals additionally received irradiated glucose-solution instead of drinking water . Results did not indicate any mutagenic activity of the irradiated diet on the histidine-auxotroph strain of Salmonella typhimurium used in the assay.

Nucleic Acids Res, 1975 Apr, 2(4), 545 - 54
Interaction between phosphoribosyltransferase and purified histidine tRNA from wild type Salmonella typhimurium and a derepressed hisT mutant strain; Deeley RG et al.; We have examined the interaction between phosphoribosyltransferase and purified tRNA-His from the wild type strain of Salmonella typhimurium, LT-2, and the histidine regulatory mutant hisTl504 . Histidyl-tRNA from the mutant strain functions normally in protein synthesis but is defective in its role in the repression mechanism of the histidine operon . Phosphoribosyltransferase has been suggested as a possible aporegulator for this operon and as such might be expected to interact abnormally with tRNA-His from hisT1504 . In these studies we have been unable to detect any difference between the affinities of phosphoribosyltransferase for tRNA-His from LT-2 or hisT1504, and thus we conclude that if the complex between phosphoribosyltransferase and histidyl-tRNA does function in regulation, the defect in the hisT1504 mutant must influence the interaction of the complex with some other regulatory element.

J Bacteriol, 1975 Apr, 122(1), 171 - 6
Gentic mapping of Salmonella typhimurium peptidase mutations; Miller CG; The map positions of three loci, each specifying a different peptidase, have been determined in Salmonella typhimurium . Mutations in pepN (leading to loss of peptidase N {1974} are co-transducible with pyrD . The order of markers in this region is put pyrD pepN . Mutations in pepA (leading to loss of peptidase A {1974} are co-transducible with pyrB and argI . The relative orientation of these markers is pepA argI pyrB . Mutations in pepDP (leading to loss of dipeptidase, peptidase D) are co-transducible with proBA and gxu . The order of these markers is pepD gxu pro.

J Bacteriol, 1975 Apr, 122(1), 106 - 9
Effect of aeration on minimal medium recovery of heated Salmonella typhimurium; Gomez RF et al.; The effect of presence or absence of air on minimal medium recovery of heated Salmonella typhimurium was investigated . It was determined that the expression of minimal medium recovery is not only dependent on heat and a nutritionally complex medium but also on air . Unlike in the presence of air, in the presence of nitrogen, cells were able to recover their ability to grow on Trypticase soy agar enriched with 0.5% yeast extract (TSY) when incubated in TSY broth . It was established that in the presence of nitrogen the number of heat-TSY- induced, single-straneded breaks in deoxyribonucleic acid (DNA) were less than in the presence of air . Furthermore, the DNA breaks in nitrogen were repaired, whereas DNA breaks in air were not . The ability of cells to grow on TSY agar corresponded well with their ability to repair damage to DNA.

Mutat Res, 1975 Apr, 31(2), 97 - 102
Quantitative relationship between carcinogenicity and mutagenicity of polyaromatic hydrocarbons in Salmonella typhimurium mutants; Teranishi K et al.; Mutagenic activities of various polyaromatic hydrocarbons (PAHs) in air pollutants, which are different in carcinogenic activities from each other, were examined with a set of four strains of Salmonella typhimurium (TAI535 series; deep rough strains without excision repair) . All the compounds tested were converted to frameshift mutagens when they were metabolized by rat liver homogenate . There was a clear quantitative correlation between carcinogenicity and mutagenicity of PAHs tested in strain TAI538 using the rat liver enzyme induced with both dibenz(a,h)-anthracene and phenobarbital . On the other hand, such a correlation was not obvious in strain TAI537.

Appl Microbiol, 1975 Apr, 29(4), 448 - 50
Stability of bacterial mutants in saline; Kropinski AM; By storage in 1% NaCl, genetically characterized strains of Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa were stable for more than 1 year at 4 C . This method of preservation was more effective than maintenance of the strains in stab culture.

Mutat Res, 1975 Apr, 31(2), 87 - 95
Microsomal activation to mutagens of antischistosomal methyl thioxanthenones and initial tests on a possibly non-mutagenic analogue; Hartman PE et al.; Five methylthioxanthenone and methylbenzothiopyranoindazole analogues, including lucanthone (Miracil D), are non-mutagenic for Salmonella typhimurium but are activated to mutagens by a rat liver microsome preparation . Hydroxymethyl analogues, including hycathone (Etrenol), are mutagenic in the absence of microsomes . It seems reasonable to assume that the hydroxymethyl derivatives are the more proximal mutagens and that Salmonella is unable to carry out the hydroxylation necessary for mutagen activation . During the pase 24 years, several million patients with schistosomiasis have been treated with lucanthone, and in recent years about 700 000 persons with hycanthone . The possible long-term deleterious effects of these agents for man even now remain to be determined . Our studies indicate that particular modifications in the structure of thioxanthenones drastically alter their mutagenicity . One apparently non-mutagenic thioxanthenone has been found . A number of the less mutagenic compounds also exhibit decreased acute toxicity in the mouse while retaining appreciable antischistosomal activity, suggesting that genetic and schistosomicidal activities may be dissociated from each other.

Mutat Res, 1975 Apr, 28(1), 31 - 5
Mutagenicity testing with Salmonella typhimurium strains . II . The effect of unusual phenotypes on the mutagenic response; Chen CC et al.; The enhanced sensitivity of some Salmonella typhimurium strains to the mutagenic action of a number of chemicals appears to be due to the defect in the uvrB gene product and not to an inability to produce H-2-S or to the absence of formic acid hydrogenlyase which also characterizes these strains.

J Immunol, 1975 Apr, 114(4), 1323 - 8
Mechanism of the suppressive effect of interferon on antibody synthesis in vivo; Brodeur BR et al.; Mouse interferon preparations significantly suppress the in vivo antibody response to sheep red blood cells (SRBC), a thymus-dependent antigen, and to Salmonella typhimurium lipopolysaccharide (LPS), a thymus-independent antigen . It is also possible to effect the late responses of antigen sensitive "memory" cells observed during secondary immunization by administration of interferon prior to primary immunization . The immunosuppressive activity of interferon was time- and dose-dependent . Maximum suppression was produced when animals were given 1.5 times 10-5 units of interferon between 4 and 48 hr before antigenic stimulation . These findings suggested that interferon affects some early event(s) in the process of antibody synthesis which might be related to the general inhibitory effect of interferon on rapidly dividing cells and viral m-RNA translation . In addition, the use of nonadherent spleen cell cultures from interferon-treated mice, immunized in vitro with a thymus-independent antigen, indicated that in this situation the inhibitory effect of interferon was due to an action on B lymphocytes . A variety of soluble "suppressive" factors are secreted by T cells as a consequence of activation by mitogens or specific antigens in vitro . Since T cells are recognized as one of the sources of interferon, it is suggested that interferon should be investigated as a suppressor T cell-produced lymphokine which can regulate B cell expression.

Res Commun Chem Pathol Pharmacol, 1975 Mar, 10(3), 419 - 29
Aflatoxicol H1: a major metabolite of aflatoxin B1 produced by human and rhesus monkey livers in vitro; Salhab AS et al.; Among the major metabolites of aflatoxin B1 produced by human and monkey livers in vitro is a derivative with the ketone carbonyl on the cyclopentane ring reduced to a secondary alcohol, and a hydroxyl introduced onto the carbon beta to the alcohol group . The metabolite was formed from aflatoxin B1 at a level similar to that of aflatoxin M1.Both the microsomal hydroxylase and the cytoplasmic reductase systems are required for its formation . Bioassay using chicken embryos and a mutant of Salmonella typhimurium revealed no toxicity . This newly identified metabolite was named aflatoxicol H1.

Onderstepoort J Vet Res, 1975 Mar, 42(1), 15 - 24
Inhibition of macrophage migration in Salmonella immunity; Cameron CM et al.; Protein antigens were prepared from rough strains of Salmonella typhimurium and S . dublin by phenol and veronal-buffer extraction . It was shown that the in vitro migration of peritoneal exudate cells from guinea pigs that were immunized with rough avirulent mutants could be inhibited effectively with these antigens . The cells obtained from S . typhimurium-immunized guinea pigs were also sensitive to S . dublin antigens and vice versa . A degree of sensitivity and inhibition could be demonstrated consistently in a group of immunized guinea pigs . However, the variation in samples, even from among individual animals that had survived challenge, was so great that it precludes the use of the macrophage migration technique as a routine standard assay procedure for immunity.

Parazitologiia, 1975 Mar-Apr, 9(2), 158 - 64
{A histologic study of Ceratophyllus consimilis Wagn . fleas infected by the agent of murine typhus (Salmonella typhimurium)}; Vashchenok VS et al.; Histological studies of C . consimilis infected with S . typhimurium have shown that the microbes are preserves along the whole extent of the alimentary canal, expecially in the midgut and pyloric portion . Bacteria are concentrated in the gastral cavity; in addition, they were found to penetrate the alimentary epithelium cells and pyloric valve tissue . The number of microbes and their distribution in the intestine undergo great variations that depends largely on the insects feeding rhythm . During bloodsucking a "lavenment" of the alimantary canal takes place; as a result, numerous microbes accumulated here are periodically excreted outside . The infection with Salmonella typhimurium is often accompanied by pathological changes in fleas tht is expressed in the destruction of the midgut epithelium and pyloric valve tissue.

J Gen Microbiol, 1975 Mar, 87(1), 37 - 51
Reversible inactivation of the isocitrate dehydrogenase of Escherichia coli ML308 during growth on acetate; Bennett PM et al.; During aerobic growth of Escherichia coli ML308 on acetate as sole carbon source, the apparent synthesis of isocitrate dehydrogenase was repressed relative to cultures on other carbon sources, such as glucose, which do not employ the glyoxylate bypass as an anaplerotic sequence . When cells were removed from an acetate medium, or when compounds were added which made the operation of the glyoxylate bypass unnecessary, the activity of isocitrate dehydrogenase rapidly increased 3- to 4-fold but fell again on restoration to an acetate medium . Changes in activity were rapid and, furthermore, could be demonstrated in the absence of protein synthesis . It is thus improbable that the mechanism involved degradation or de novo synthesis of the enzyme protein . Oxaloacetate and glyoxylate showed concerted inhibition of isocitrate dehydrogenase which could be relieved by dialysis . Because extracts of low enzyme activity, derived from acetate-metabolizing cells, could not be stimulated by dialysis or by addition of a wide range of metabolites, it is unlikely that low molecular weight, freely dissociable effectors were responsible for stimulation or inhibition of activity . Control of isocitrate dehydrogenase permitted the efficient utilization of acetate as sole source of carbon and energy but perserved the capacity of the cell to respond rapidly to an improvement in nutritional conditions . A limited survey showed that the mechanism is common but not universal among strains of E . coli and occurs in at least one strain each of Klebsiella aerogenes, Salmonella typhimurium and Serratia marcescens.

J Gen Microbiol, 1975 Mar, 87(1), 1 - 10
Mutations in Salmonella typhimurium conferring resistance to Felix O phage without loss of smooth character; MacPhee DG et al.; Several mutants obtained from smooth Salmonella typhimurium strains by selection for resistance to Felix O (FO) phage {whose receptor site includes the N-acetylglucosamine branch of the lipopolysaccharide (LPS) core} were smooth in cultural properties, antigenic character and phage sensitivity pattern (except for their FO resistance) . However, the affected genes of several such 'FOR' (FO-resistant) mutants were shown by transduction of map in the short cysE-pyrE segment, which includes nearly all known rfa genes responsible for synthesis of LPS core . All of seven FOR mutants differed from their parents, and resembled rfa mutants with defects in the deeper part of the LPS core, by increased sensitivity to various antibiotics . One FOR mutant was non-virulent (LD50 greater than 10-7, compared with smaller than 100 for its parent); LT7 derivatives given this FOR gene by co-transduction with cysE+ were likewise non-virulent . It is inferred that FOR mutations affect the assembly of the inner part of the LPS core, perhaps causing incomplete blocks in glycosyl transferase reactions.

Res Vet Sci, 1975 Mar, 18(2), 165 - 70
Experimental infection of cockerels with Salmonella typhimurium; Brown DD et al.; Six-month-old SPF Brown Leghorn cockerels were experimentally infected per os with S typhimurium (1 times 1010) and slaughtered at intervals up to 42 days following infection . Observations were made on the clinical pathology, bacteriology and serology during the course of infection and extensive bacteriological examinations were undertaken after post mortem examination.

Mutat Res, 1975 Mar, 27(3), 299 - 306
Induction of base-pair substitution and frameshift mutations in wild-type and repair-deficient strains of Salmonella typhimurium by the photodynamic action of methylene blue; Imray FP et al.; Induction of back mutations to prototrophy by methylene blue (MB)-sensitized photodynamic (PD) treatment has been studied in wild-type and repair-deficient strains of Salmonella typhimurium carrying either the base-pair substitution mutation hisG46 or the frameshift mutation hisD30529 We found that reversion of the hisG46 mutation was increased in a strain carrying a uvrB deletion and decreased in a strain carrying a recA-type mutation . Reversion of the hisD3052 (frameshift) mutation, on the other hand, was decreased in both uvrB deletion and recA-type strains . The former results are consistent with the hypothesis that the majority of MB-sensitized PD-INDUCED BASE-PAIR SUBSTITUTION MUTATIONS ARIse by a mechanism similar to that currently believed to be involved in UV mutagenesis . The latter results suggest that PD-induced frameshift mutations may arise in some other way, and two possible mechanisms involving sequential action of the excision repair and recombinational repair pathways are considered.

Cancer Res, 1975 Mar, 35(3), 644 - 51
In vitro metabolism and microsome-mediated mutagenicity of dialkylnitrosamines in rat, hamster, and mouse tissues; Bartsch H et al.; Rates of conversion of 14C-labeled dimethyl-and diethylnitrosamine by rat and hamster tissue slices to 14CO2 and/or into mutagenic reactants were measured using Salmonella typhimurium G-46 r TA 1530 and fortified tissue fractions in vitro . A correlation between the CO2 production from dimethyl- or diethylnitrosamine in liver or lung and the organ distribution of induced tumors in vivo was observed . As an exception, hamster lung, which is a major target organ in diethylnitrosamine carcinogenesis, did not convert this nitrosamine into metabolites mutagenic for S . typhimurium TA 1530 although the 14CO2 production in vitro was even higher than in hamster liver . The effect of pretreating rats, hamsters, and mice with phenobarbitone on the mutation frequency produced by dimethyl-or diethylnitrosamine in in vitro assays was determined . The relationship between the site of metabolic activation, mutagenicity, and carcinogenicity of the dialkylnitrosamines and the effect of enzyme inducers are discussed.

J Bacteriol, 1975 Mar, 121(3), 814 - 22
Control of expression of the pyr genes in Salmonella typhimurium: effects of variations in uridine and cytidine nucleotide pools; Schwartz M et al.; The differential rate of synthesis of five of the pyrimidine biosynthetic enzymes coded for by pyrB-F, and the endogenous concentrations of the individual pyrimidine nucleotides were determined in specially constructed mutants of Salmonella typhimurium . In the mutants employed the different pyrimidine nucleotide pools may be manipulated individually during exponential growth . The results obtained indicate the following . (i) The expression of pyrB, pyrE, and pyrF is controlled by a uridine nucleotide in a noncoordinate manner . (ii) The expression of pyrC and pyrD is regulated predominantly by a cytidine nucleotide . Under all conditions investigated, their expression seems to be coordinated, even though the genes are not contiguous on the chromosome . (iii) The low-molecular-weight effectors involved in controlling the expression of the pyr genes are neither uridine 5'-monophosphate nor cytidine 5'-monophosphate, but rather the corresponding di- or triphosphates.

J Gen Microbiol, 1975 Mar, 87(1), 11 - 9
Salmonella typhimurium mutations conferring resistance to Felix O phage without loss of smooth character: phage attachment and immunochemical and structural analyses of lipopolysaccharides; Lindberg AA et al.; Salmonella typhimurium mutants, called Felix O-resistant (FOR), selected for resistance to phage Felix O (FO) which has its receptor in the core lipopolysaccharide (LPS), retain most of the properties of the smooth parent strain (MacPhee, Krishnapillai, Roantree & Stocker, 1975) . LPS extracted from one parent and two FOR strains by the phenol-water and the phenol-chloroform-light petroleum methods have been subjected to passive haemagglutination inhibition and methylation analysis . The amount of LPS, the amount of O-specific sugars in the LPS, and the average length of the O chains were almost the same in parent and mutant strains . Neither passive haemagglutination nor methylation analysis revealed the presence of incomplete cores in the mutant strains . Determination of the rates of attachment of P22 (receptor in O chain) and FO phages to whole bacteria of the same strains also suggested there is as much O-chain material in the FOR strains as in the parent strain . The data suggest that the FOR strains are the result of a mutation in the synthesis of the core, leaving few, if any, completed cores accessible to the FO phage.

Infect Immun, 1975 Mar, 11(3), 592 - 4
Stimulation of phagocytic activity in the reticuloendothelial systems of mice by lipid A complexed with homologous or heterologous proteins; Nakano M et al.; Heterologous proteins are more suitable carriers than homologous proteins for the expression of endotoxic activity of lipid A prepared from the lipopolysaccharides of Salmonella typhimurium SL1102 (Re form) to stimulate the reticuloendothelial system of mice.

J Biol Chem, 1975 Feb 25, 250(4), 1563 - 70
Threonine deaminase from Salmonella typhimurium . Relationship between regulatory sites; Decedue CJ et al.; Kinetic analysis of the biosynthetic threonine deaminase, EC 4.2.1.16, from Samonella typhimurium yields hyperbolic substrate saturation curves in the absence of, and higher order substrate saturation curves in the presence of, L-isoleucine . L-Valine reverses this effect of L-isoleucine by restoring the hyperbolic substrate saturation curves . The inhibition of enzyme activity and the reversal of valine stimulation is a function of a second order concentration of L-isoleucine, whereas antagonism of inhibition is a function of first order concentration of valine . The antagonistic effects on enzyme activity of L-isoleucine and of L-valine appear as competitive in diagnostic plots . Threonine deaminase possesses two L-isoleucine binding sites (Kd equals 3.6 muM) and one L-valine binding site (Kd equals 26 muM); the binding of these ligands appear competitive . Exclusion of L-valine requires the binding of 2 molecules of L-isoleucine whereas binding of a single L-valine molecule prevents the binding of 2 L-isoleucine molecules . Cooperative binding of L-isoleucine is not observed under any of the conditions tested . Two cases, expressed in terms of modified Adair equations and based upon the assumption that L-threonine also serves as an activator ligand which binds to the L-valine site, are presented . Case I states that liganding of the activator sites must percede substrate-binding at the active site, and Case II states that the activator site liganding is required solely for reactivation of the L-isoleucine-inhibited enzyme . Analysis of kinetic data by a curve-fitting process suggests that Case II described the relationship between the activator site and the L-isoleucine sites . An enzymatically inactive derivative of threonine deaminase, prepared by reduction with borohydride, binds isoleucine and valine in a manner similar to native holoenzyme . Binding of L-threonine and L-valine to the derivatized enzyme is competitive . The Kd for threonine binding is 3 mM, which is in excellent agreement with the Kd determined by the curve fitting process . It is concluded that the modulation of threonine deaminase activity is wrought by interaction between inhibitor sites and an activator site rather than inhibitor and active sites and that induced transitions rather than concerted transitions more adequately describe the underlying regulatory principle.

Eur J Biochem, 1975 Feb 21, 51(2), 449 - 57
Glyceraldehyde phosphate at the reducing terminus of Salmonella Q haptens . Salmonella montevideo; Gmeiner J; The O antigen polysaccharide of Salmonella montevideo was isolated from a core-defective mutant by the phenol/water procedure, and was suspected to contain phosphomonester and cyclic phosphodiester at its reducing end in anology to the O hapten from Salmonella typhimurium (Kent and Obsborn, 1968 . Therefore, it was chromatographed on a DEAE-cellulose column . Whereas one part eluted with water the other part of the polysaccharide could only be eluted with buffer . Both fractions were further purified on Sephadex G100 and contained mannose, glucose, N-acetylglucosamine and phosphate in a molar ratio of 4:1:1: less than 0.1 . In order to specifically label the reducing end phosphate was removed enzymatically, or the presumed cyclic diester was cleaved by mild hydrolysis, and the fractions were reduced with sodium horo{3H}hydride . Both fractions yield mainly {3H}glycerol after hydrolysis and paper chromatogaphy . In addition, {3H}mannitol and {H}monohydroxyacetone could be identified by paper chromatography and were concluded to be the result of phosphate migration and beta-elimination reactions taking place during the isolation procedure and the various treatments prior to sodium boro{3H}hydride reduction . These findings in addition to periodate oxidation studies indicated that the O antigen polysaccharide of Salmonella montevideo had glyceraldehyde phosphate at its reducing end . From the incorporation of 3H into the polysaccharide the O antigen was calculated to consist of about 19 repeating units of 6 sugar residues each.

Eur J Biochem, 1975 Feb 21, 51(2), 343 - 52
Asymmetrical distribution and artifactual reorientation of lipopolysaccharide in the outer membrane bilayer of Salmonella typhimurium; Muhlradt PF et al.; Labelling of cell walls or outer membranes from Salmonella typhimurium with ferritin-conjugated antibodies directed against the polysaccharide moiety of the lipopolysaccharide gave the following results: 1 . Cell walls or outer membranes from which the mucopeptide had been removed by lysozyme digestion at 0 degrees C carried the label on the outer face of the membrane . 2 . When the murein layer was removed by either lysozyme or trypsin at physiological temperature (25-37 degrees C) subsequent labelling showed the lipopolysaccharide to be present on both membrane faces . 3 . This reorientation could be achieved by a 1-min treatment of the membranes at 37 degrees C . 4 . Glutaraldehyde fixation of the outer membranes did not entirely prevent but somewhat inhibited the temperature-induced reorientation process . 5 . The same reorientation phenomenon was observed in lysozyme spheroplasts, which were prepared at 37 degrees C and were subsequently lysed in hypotonic medium at 0 degrees C . These observations are discussed as evidence for a transmembrane movement of lipopolysaccharide, which only takes place in areas where the mucopeptide layer is defective, and only when the temperature is sufficiently high to allow such movement.

J Biol Chem, 1975 Feb 10, 250(3), 877 - 82
The subunit structure of alpha-acetohydroxyacid isomeroreductase from Salmonella typhimurium; Hofler JG et al.; Alpha-Acetohydroxyacid isomeroreductase from Salmonella typhimurium has a native molecular weight of 220,000 . The constituent polypeptide chains exhibit anomalous but unimodal electrophoretic migration on sodium dodecyl sulfate-urea polyacrylamide gels . The subunit molecular weight, determined by sedimentation equilibrium in 6 M guanidine hydrochloride, is 57,000 . The apparent tetrameric nature of the native enzyme was confirmed by determining the types of oligomers formed upon cross-linking with dimethylsebacimidate . Analysis of tryptic peptides suggests that the polypeptide chains have an identical amino acid sequence . Carbohydrate analysis, ultraviolet absorption spectrum, and atomic absorption spectrum are consistent with the lack of cobalamine and cobalt . The Michaelis constants are as follows: alpha-acetolactate, 2.9 x 10-4 M; alpha-aceto-alpha-hydroxybutyrate, 7.8 x 10-4 M; NADPH, 1.5 x 10-5 M; Mg2+, 7.7 x 10-4 M . The catalytic constants (molecules of substrate catalyzed per min per molecules of enzyme) for alpha-acetolactate and alpha-aceto-alpha-hydroxybutyrate are 1,100 and 4,700, respectively . Comparative tryptic peptide analysis and immunological analysis show that alpha-acetohydroxyacid isomero-reductase and biosynthetic L-threonine deaminase bear no structural relationship and therefore rule out a "shared structure" hypothesis for the putative involvement of L-threonine deaminase in the synthesis of alpha-acetohydroxyacid isomeroreductase.

Lancet, 1975 Feb 8, 1(7902), 319 - 22
Person-to-person spread of Salmonella typhimurium after a hospital common-source outbreak; Steere AC et al.; In September, 1973, diarrhoea caused by Salmonella typhimurium developed in 32 people in a Maine hospital . Both epidemiological and microbiological evidence indicated that raw egg beaten in milk ("egg-nog") was responsible for the infection . However, 6 patients and 8 employees had not had egg-nog, and their illness developed after the source of infection had been recognised and removed . Most of these people had had direct contact with an infected patient, and presumably acquired the infection by person-to-person spread . It is concluded that person-to-person spread of S . typhimurium can occur in hospitals and can be a hazard to patients and staff.

Eur J Biochem, 1975 Feb 3, 51(1), 253 - 65
Purine nucleoside phosphorylase from Escherichia coli and Salmonella typhimurium . Purification and some properties; Jensen KF et al.; The purine nucleoside phosphorylases from Escherichia coli and from Salmonella typhimurium have been purified to electrophoretic homogeneity and crystallized . Comparative studies revealed that the two enzymes are very much alike . They obey simple Michaelis-Menten kinetics for their substrates with the exception of phosphate for which they show negative cooperativity . Gel filtration on Sephadex G-200 of the native enzymes revealed a molecular weight for both enzymes of 138000 plus or minus 10% . By use of dodecylsulphate gel electrophoresis a subunit molecular weight of 23700 plus or minus 5% was determined, suggesting that both enzymes consist of six subunits of equal molecular weight . When the subunits were partially crosslinked with dimethyl suberimidate before dodecylsulphate electrophoresis six protein bands were observed in agreement with the proposed oligomeric state of the enzyme, consisting of six subunits of equal molecular weight . Analysis of the amino acid composition also indicates that the subunits are identical . 6M guanidinium chloride dissociates the enzymes; association experiments with native and succinylated enzymes suggested that only the hexameric form is active . Both enzymes could be dissociated into subunits by p-chloromercuribenzoate; this dissociation is prevented by the substrates: the nucleosides, the pentose 1-phosphates, and mixtures of phosphate and purine bases.

Mutat Res, 1975 Feb, 31(1), 39 - 42
Mutagenicity of sodium hypochlorite for Salmonella typhimurium; Wlodkowski TJ et al.; Sodium hypochlorite, a standard household item, induces base-substitution mutations in Salmonella typhimurium . Because of its potent bactericidal effect the mutagenicity of hypochlorite could best be demonstrated by short-term exposure to this chemical followed by the addition of ascorbic acid to decompose the hypochlorite.

J Med Microbiol, 1975 Feb, 8(1), 149 - 66
A new biotyping scheme for Salmonella typhimurium and its phylogenetic significance; Duguid JP et al.; A new, two-tier system for biotyping Salmonella typhimurium gives a finer and more reliable differentiation of strains than the Kristensen scheme and is capable of future extension by the addition of new types and new tests . Strains are allocated to a primary type (1-32) by their reactions in five primary tests with Bitter's xylose medium, meso-inositol, L-rhamnose, d-tartrate and m-tartrate . Subtypes are distinguished within the primary types by reactions in ten secondary tests, which include observations for flagella and type-1 (haemagglutinating) fimbriae . Full biotypes are designated by letters indicating the subtype reactions appended to the primary-type numbers . A series of 2030 strains of S . typhimurium collected from many different sources and countries during 53 years was classified into 19 of the 32 potential primary biotypes and into 144 full biotypes . Of the series, 14% (275) were non-fimbriate inositol-nonfermenting rhamnose-nonfermenting (FIRN) strain in primary biotypes 29-32 . Most other strains were fimbriate and rhamnose fermenting . Observations on several series of cultures isolated from different human or animal sources in the same epidemic showed that the biotype characters of a strain were generally stable during its growth in the natural environment and in the unselective media used for isolation and storage . Most non-fermenting strains gave rise to fermenting mutants on prolonged incubation in the substrate-containing--and therefore selective--test medium, and false-positive results from this cause were avoided by making the definitive readings of tests after a short, carefully chosen period of incubation . A genealogical tree has been drawn to show how eighteen observed primary biotypes may have evolved from a presumed archetypal ancestor of biotype 1.

J Gen Microbiol, 1975 Feb, 86(2), 275 - 82
Polarity of the cysJIH operon of Salmonella typhimurium; Loughlin RE; Certain point and deletion mutants with lesions in the cysJ gene of Salmonella typhimurium have low levels of enzymes coded by the cysI and cysH genes . These results support the hypothesis that an operon exists comprising genes cysJ, I and H which is transcribed in the direction from cysJ to H . The nearby cysC and cysD genes do not form part of this cysJIH operon.

Infect Immun, 1975 Feb, 11(2), 365 - 70
Association of Salmonella typhimurium with, and its invasion of, the ileal mucosa in mice; Tannock GW et al.; A wild-type strain of Salmonella typhimurium and three mutant rough colonial variants of the wild type were compared for their ability to become associated with and invade the ileal mucosa of germfree and specific-pathogen-free mice . The rough-mutant strains differed from the wild type in having incomplete lipopolysaccharides lacking one or more sugars in the polysaccharide moiety . The wild-type and mutant strains also differed one from the other in the types of appendages (flagella, pili) on their surfaces . Depending upon the dosage of bacteria given, all mutant strains as well as the wild type could associate with and invade the intestinal mucosa of infected gnotobiotic mice . If the infecting dosage was high enough, at least two of the mutant strains and the wild type invade the intestinal mucosa of the specific-pathogen-free animals . O antigen, flagella, or pili do not appear to be essential for the association of S . typhimurium with the mucosal surface of the mouse ileum . O antigen on the bacterial cell surface may be important, but not essential, for invasion of the ileal mucosa.

J Bacteriol, 1975 Feb, 121(2), 485 - 90
Composition of the first enzyme of histidine biosynthesis isolated from wild-type and mutant operator strains of Salmonella typhimurium; Parsons SM et al.; The first enzyme of histidine biosynthesis in Salmonella typhimurium, adenosine triphosphate phosphoribosyltransferase (EC 2.4.2.17), has been purified from two bacterial strains containing histidine operator deletions and compared to the eenzyme from a strain that has a normal operator . The enzymes isolated in different ways also are compared . Evidence as to the separateness of the operator and first structural gene or covalent modification of the first enzyme was sought . Specific activity, histidine feedback inhibition, amino acid analysis, discontinuous-gel electrophoresis, and gel filtration of the native enzyme, and Ouchterlony double-immunodiffusion tests were carried out . The purified enzyme contains little phosphorous and has five cysteine residues per subunit, which all are readily titratable . No evidence for differences in the enzyme preparations was obtained . Thus, no evidence for overlap of the histidine operator with the first structural gene was obtained.

J Bacteriol, 1975 Feb, 121(2), 583 - 93
Isolation of super-repressor mutants in the histidine utilization system of Salmonella typhimurium; Hagen DC et al.; Two super-repressor mutations in the histidine utilization (hut) operons of Salmonella typhimurium are described . Cells bearing either of these mutations have levels of hut enzymes that do not increase above the uninduced levels when growth is in the presence of either histidine or the gratuitous inducer imidazole propionate . Both mutations lie in the region of the gene for the hut repressor, hutC, and reverse mutations of both are to the constitutive (repressor-negative) rather than to the inducible (wild type) phenotype . In hybrid merodiploid strains the super-repressor mutations are dominant over either wild-type (hutC+) or repressor-negative (hutC-) alleles . Whereas both super-repressor mutations cause the uninducible synthesis of hut enzymes, the degree of repression is different . One mutation causes repression of enzyme synthesis in one of the two hut operons to a level below the basal, uninduced level of wild-type cells . The other mutation causes repression to a lesser degree than in wild-type cells, so that the hut enzymes are present at a level above the normal basal level; this partially constitutive synthesis is greater for the enzymes of one of the hut operons than for the enzymes of the other . Thus, both mutations apparently result in repressors with altered operator-binding properties, in addition to altered inducer-binding properties.

Lancet, 1975 Feb 1, 1(7901), 235 - 40
Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin; McHugh GL et al.; A strain of Salmonella typhimurium appeared sequentially in three patients in a burn unit, and epidemiological study suggested the occurrence of person-to-person spread . This organism was responsible for both colonisation and invasive infection in these patients whose burn surfaces were receiving topical treatment with 0.5% silver nitrate (AgNO3) solution . The antibiotic and metal ionsusceptibility pattern of this strain of S . typhimurium was unique and disturbing: resistant to silver nitrate, mercuric chloride, ampicillin, chloramphenicol, tetracycline, streptomycin, and sulphonamides . This pattern of multiple resistances could be transferred by invitro mating experiments to sensitive recipient strains of Escherichia coli and S . typhimurium . Further transfer of these resistances could be consumated between different strains of E . coli . A survey of other salmonella strains isolated from patients in this hospital without thermal burns did not reveal this pattern of resistance . Also, strains of S . typhimurium, isolated elsewhere and showing simultaneous resistance to both ampicillin and chloramphenicol, were not resistant to AgNO3 in vitro . The very real danger of this strain of S . typhimurium in burn units stems from its resistance to the two most effective antibiotics (ampicillin and chloramphenicol) available for systemic therapy; and this threat may be compounded through the selection effected by the widespread topical use of AgNO3 solutions and sulphonamide preparations on burned surfaces.

J Biol Chem, 1975 Jan 25, 250(2), 609 - 16
Deoxycytidine triphosphate deaminase of Salmonella typhimurium . Purification and characterization; Beck CF et al.; Deoxycytidine triphosphate deaminase (EC 3.5.4., dCTP aminohydrolase) of Salmonella typhimurium LT2 has been pruified 500-fold . The reaction requires the presence of Mg-2plus, Mn-2plus, Ca-2lus, or Co-2plus . Kinetics of the reaction with varying Mg-2plus concentrations, keeping the concentration of dCTP constant, suggests that the true substrate of the reaction is MgdCTP . The dependence of the rate of reaction on dCTP concentration in the presnece of 5-fold excess of Mg-2plus is sigmoid, with a Hill coefficient of 1.7 . The enzyme is specifically inhibited by dTTP and dUTP . In the presence of increasing dTTP concentrations the sigmoidicity of the substrate saturation curves increases . With 0.2 and 0.4 mM dTTP the Hill coefficients are 2.6 and 3.0, respectively . Despite several attempts no dissociation of the substrate site and the inhibitor site of the enzyme was achieved.

S Afr Med J, 1975 Jan 11, 49(2), 55 - 6
Typhoid cardiac involvement; Mokhobo KP; Three cases of typhoid cardiac complications are reported . Salmonella typhi was the aetiological agent in all three; The discovery of 3 patients over a period of 18 months merits special interest, especially since typhoid fever is endemic in the area concerned . The significance of the complication reported here is further enhanced by absence of similar specific cases in the English literature dealing with cardiac salmonellosis . One of the cases described in this article, the only fatality of the series, developed a rhythm disturbance identical with that of a patient whose myocardial abscess was due to Salmonella typhimurium . The rarity of typhoid cardiac complications may be deceptive; The septicaemic disturbance may mask it and one must note that cardiac salmonellosis is reported from developed countries, where typhoid fever is a rarity.

Arq Inst Biol (Sao Paulo), 1975, 42, 233 - 8
{Blood cultures-bacteriological and drug resistance culture (author's transl)}; Moreno G et al.; Blood cultures of 24 patients from the Hospital das Clinicas da Faculdade de ciencias Medicas e Biologicas de Botucatu showed a prevalence of gram-negative isolates (83%) over gram-positive (16%) . Among the microorganisms Salmonella typhimurium was the most frequent (25%) followed by Klepsiella sp . (21%) and Escherichia coli (17%) . It was also observed that the main cuase of death was the largest occurrence of Salmonella typhimurium and Pseudomonas aeruginosa among the isolates . Regarding drug resistance gentamycin revealed more active than other antibiotic tested.

Immunol Commun, 1975, 4(5), 429 - 42
Phagocytosis as a surface phenomenon . V . Contact angles and phagocytosis of rough and smooth strains of Salmonella typhimurium, and the influence of specific antiserum; Cunningham RK et al.; The angle made by a drop of saline in contact with a monolayer of Salmonella typhimurium or phagocytic cells, the contact angle, is a measure of their relative interfacial tension, and is predictive of a successful phagocytosis . Smooth strains of S . typhimurium possess a contact angle lower than the phagocytic cells and resist phagocytosis . Rough strains have an angle higher than the phagocytes and are readily engulfed . The lower contact angle of smooth strains can be increased by treatment with specific antibody resulting in more efficient phagocytosis.

Z Allg Mikrobiol, 1975, 15(6), 447 - 56
Mode of growth and division of Salmonella typhimurium; Shannon KP et al.; A temperature-sensitive strain (HD 20) of Salmonella typhimurium is described . At restrictive temperature this strain shows an envelope alteration and a defect in division associated with an increase in cell diameter . On a shift to 42 degrees C there is residual division for ca . 30 min and then no further increase in cell number . In minimal medium (MM) at 42 degrees C cell diameter remains unchanged for about one mass doubling and then increases . From measurements of cell elongation, it is concluded that such increases in diameter occur because cell volume increases exponentially at 42 degrees C but increases in the rate of elongation occur for only a short period and then elongation rate becomes constant . This conclusion is supported by the observation that HD 20 cells show no increase in diameter at 42 degrees C when cultured in media supplemented with sucrose and Mg++; normal increases in elongation rate occur in such media . A model which fits the experimental data has been constructed . This model has two main features namely (1) the elongation of individual cells is linear with the rate of elongation doubling close to division and (2) such doublings in elongation rate are linked to division such that division cannot occur if elongation rate has not doubled shortly before . In the mutant it is proposed that only a few doublings in elongation rate occur at 42 degrees C and these are responsible for the residual division . The model fits the data for cultures shifted to 42 degrees C in MM or in yeast extract casamino acids MM (YE Cas MM) and for cultures shifted to 42 degrees C and shifted up from MM to YE Cas MM . The observations on these medium shifted cultures suggest that the activity of growth zones responsible for elongation is medium dependent.

Mol Gen Genet, 1975, 138(2), 113 - 26
Transduction by phage P1CM clr-100 in Salmonella typhimurium; Mojica T; Phage P1 does not adsorb to S . typhinurium wild type cells . It does adsorb to rough derivatives including strains with mutations in the galE gene . Phage strain P1CM clr-100 can be efficiently propagated in S . typhimurium derivatives, either by induction of a lysogene, or by lytic infection . Phage P1 lysates are able to mobilize genetic markers in a generalized fashion . The transduction system is essentially identical to that in Escherichia coli, except that CaCl2 is not required for efficient adsorption . Two regions of the S . typhimurium chromosome were mapped by P1-mediated transduction . Several examples of genes linked by P1, and unlinked by P22, are presented . The relative efficiency of P1 over P22 in transduction was not determined, however . Data presented indicate unambigously that the gene order for the trp region is: his .. . dad A-hem A-trp-pyrF .. . pyrC but known markers in between were not used . The gene order for the cys A region was determined to be as follows: pheA .. . purC-cys A-trz A-pts-dsd-aro D-purF .. . his, and special mapping problems for this region are discussed.

Mol Gen Genet, 1975, 138(1), 41 - 52
The role of methionine transport-defective mutations in resistance to methionine sulphoximine in Salmonella typhimurium; Betteridge PR et al.; Two classes of Salmonella typhimurium mutants resistant to inhibitory methionine analogues and defective in methionine transport have been examined . A mutant of the first class, resistant to alpha-methylmethionine, was shown by conjugation analysis to possess a single mutation in the metP gene which specifies a methionine transport system . Mutants of the second class, resistant to alpha-methylmethionine and methionine sulphoximine, possess two mutations . One is in the metP gene, which accounts for resistance to alpha-methylmethionine, and the other is in a gene designated glnP which results in reduced L-glutamine transport . Both of these mutations are required for resistance to methionine sulphoximine . A transduction analysis of three metP mutations was performed, based on the fact that they prevent growth of methionine-requiring strains on D-methionine . Two of the mutants are closely linked and therefore probably in the same gene, whereas the third mutant might be in a different gene.

Acta Biochim Pol, 1975, 22(2), 185 - 94
Alkylated cytosine nucleosides: substrate and inhibitor properties in enzymatic deamination; Krajewska E et al.; Cytosine nucleoside deaminase (EC 3.5.4.5) from Salmonella typhimurium LT2 catalyses the deamination of ribo-, deoxyribo- and arabinosyl nucleosides of cytosine alkylated at the C-5, but not at the N3 or exocyclic N4, of the pyrimidine ring . The enzyme was inert towards analogues etherified at the 3'-OH and 5'-OH of the sugar ring; it was active against the 2'-O-methyl derivative of cytidine, but not arabinosycytosine . The N4-and 5'-O-alkyl non-substrate analogues competitively inhibited deamination of deoxycytidine and arabinosylcytosine, the most inhibitory being 5'-O-methylarabinosylcytosine . The alpha anomer of 5'-ethyldeoxycytidine, the 2,2'-anhydro derivative of cytidine, and the 3'-O-alkyl derivatives were neither substrates nor inhibitors . The presence of cytidine deaminase was demonstrated in both granulocytes and lymphocytes from human peripheral blood . The specificity of this enzyme differed significantly from that of the bacterial enzyme, a finding of some relevance in relation to the frequently encountered intracellular deamination of therapeutically active arabinosylcytosine to the inactive arabinosyluracil.

Arch Toxicol, 1975, 33(3), 225 - 40
Mutagenic activity of cyclophosphamide, ifosfamide, and trofosfamide in different genes of escherichia coli and salmonella typhimurium after biotransformation through extracts of rodent liver; Ellenberger J et al.; Experiments are performed to compare the mutagenic properties of the three phosphamide esters of nitrogen mustard, cyclophosphamide (CP), ifosfamide (IF), and trofosfamide (TF), in different bacterial systems . The systems include forward mutations leading to resistance against 5-methyltryptophan (MTR) and from galR-s18 to gal-+ in Escherichia coli 343/113, back mutations from arg56 to arg-+ in Escherichia coli 343/113 and back mutations from hisG46 to his-+ in Salmonella typhimurium TA1535 . CP, IF, and TF are not mutagenic per se . After biotransformation through isolated rodent liver homogenates (S-9 fraction) all three compounds exhibit mutagenic activity in the order CP smaller than IF smaller than TF . Specific activating potential of mouse liver extracts is higher than that of rat liver . Except for back mutations in S . typhimurium TA1535, all mutation systems tested show a similar pattern of induction after treatment with CP, IF, and TF . However, because gal-+ mutations are not induced by CP under conditions where arg-+ and MTR are induced, it is suggested that more than one mutational system be used in routine mutagenicity testing.

Res Vet Sci, 1975 Jan, 18(1), 94 - 9
Studies on the development of chloramphenicol resistance in Salmonella typhimurium; Wray C et al.; Chloramphenicol therapy of acute and chronic Salmonella typhimurium infection in mice did not lead to the development of chloramphenicol resistant mutants of this organism . However, chloramphenicol resistant organisms were readily produced in vitro . Transfer of chloramphenicol resistance from a donor strain of Escherichia coli X12 to a suitable recipient strain of S typhimurium 5235 occurred readily in the intestine of 15 out of 20 conventional mice, following oral administration of large doses of these strains supplemented by chloramphenicol therapy . When a similar system was used in untreated animals, only a small number of chloramphenicol resistant S typhimurium were isolated from three out of 18 mice . The virulence of chloramphenicol resistant S typhimurium produced in vitro and in vivo was similar to that of the sensitive parent strain.

J Immunol, 1975 Jan, 114(1 Pt 2), 388 - 93
Activation of guinea pig macrophages by bacterial lipopolysaccharide requires bone marrow-derived lymphocytes; Wilton JM et al.; The activation of guinea pig peritoneal macrophages by Salmonella typhimurium lipopolysaccharide (LPS) was studied by using 14C-glucosamine uptake . Peritoneal exudate cells incorporated significant amounts of 14C-glucosamine when stimulated with LPS but neither purified macrophages nor nonadherent lymphocytes by themselves incorporated glucosamine . The activation of macrophages could be restored by adding nonadherent peritoneal lymphocytes, spleen cells, and lymph node cells but not thymocytes . Removal of B lymphocytes abolished the restorative capacity from active lymphoid cell populations . In contrast, B lymphocytes would restore glucosamine incorporation by macrophages stimulated with LPS but T lymphocytes did not . In addition, cell-free supernatants from LPS stimulated B lymphocytes but not from T lymphocytes could restore glucosamine incorporation by macrophages . These experiments demonstrate that LPS does not directly activate macrophages as measured by glucosamine incorporation but stimulates B lymphocytes which in turn activate macrophages.

J Bacteriol, 1975 Jan, 121(1), 77 - 82
Genetic modification of substrate specificity of hypoxanthine phosphoribosyltransferase in Salmonella typhimurium; Benson CE et al.; Salmonella typhimurium strain GP660 (proAB-gpt deletion, purE) lacks guanine phosphoribosyltransferase and hence cannot utilize guanine as a purine source and is resistant to inhibition by 8-azaguanine . Strain GP660 was mutagenized and a derivative strain (GP36) was isolated for utilization of guanine and hypoxanthine, but not xanthine, as purine sources . This alteration was designated sug . The strain was then sensitive to inhibition by 8-azaguanine . Column chromatographic analysis revealed the altered phosphoribosyltransferase peaks for both hypoxanthine and guanine to be located together, in the same position as hypoxanthine phosphoribosyltransferase (hpt gene product) of the wild-type strain . Genetic analysis showed the sug mutation to be allelic with hpt . Therefore sug represented a modification of the substrate specificity of the hpt gene product.

J Bacteriol, 1975 Jan, 121(1), 259 - 66
Positive selection of mutants with deletions of the gal-chl region of the Salmonella chromosome as a screening procedure for mutagens that cause deletions; Alper MD et al.; We have developed a convenient and specific positive selection for long deletions through the gal region of the chromosomes of Salmonella typhimurium and Escherichia coli . Through simultaneous selection for mutations in the two closely linked genes, gal and chlA, a variety of deletions of varying length, some extending through as much as 1 min of the chromosome, could be readily obtained . Many of these deletions resulted in the loss of a gene, which we named dhb, concerned with the ability of the bacterium to synthesize the iron chelating agent enterobactin . The selection was adapted for the screening of mutagens for their ability to generate long deletions in the bacterial deoxyribonucleic acid . Forty agents were screened for this capability . Nitrous acid, previously reported to be an efficient mutagen for this purpose, increased the frequency of deletion mutations 50-fold in our system . Three others, nitrogen mustard, mitomycin C, and fast neutrons, were shown to increase the frequency of long deletions between five- and eightfold . The remainder were found to be incapable of generating these deletions.

Arch Microbiol, 1975, 102(1), 29 - 33
Differential fluorescence labelling with 5-dimethyl-aminonaphthalene-1-sulfonyl chloride of intact cells and isolated membranes in Salmonella typhimurium and Acholeplasma laidlawii; Schindler PR et al.; For fluorescence labelling intact cells and isolated cell envelopes (membranes) from Salmonella typhimurium and Acholeplasma laidlawii were treated with mixed dansylchloride-lecithin-cholesterol vesicles . This kind of dansylation, which has been supposed to be specific for cell surface proteins, produced fluorescent protein pattern after SDS-polyacrylamide gel electrophoresis only when isolated envelopes were dansylated . Acid hydrolysis of fluorescent cell envelopes of Salmonella typhimurium yielded O-dansyltryosine and epsilon-N-dansyl-lysine besides the free sulfonic acid and unidentified compounds . However, no fluorescent proteins were detectable in cell envelopes isolated from dansylated intact bacteria from Salmonella typhimurium . In accord Acholeplasma laidlawii showed only fluorescence from proteins with a molecular weight higher than 100000.

Environ Qual Saf Suppl, 1975, 4, 264 - 77
Mutagenicity assays on fluorescent whitening agents using microorganisms; Kilbey BJ et al.; Six fluorescent whitening agents (FWAs) have been re-examined for their activity as inducers of cytoplasmic petite mutants and mitotic gene conversion in diploid yeast Saccharomyces cerebisiae and reversion from auxotrophy to prototrophy in Neurospora crassa, Escherichia coli and Salmonella typhimurium . The results provide no indication that the FWAs examinded produce mutagenic changes or any other alterations in the gene material . In a recent re-examination with Salmonella using the method of Ames et al., the four examined compounds failed to elicit a mutagenic response in the presence of rat liver postmitochondrial supernatant and cofactors.

C R Seances Soc Biol Fil, 1975, 169(2), 350 - 4
{Protection by oral vaccination of mice with an avirulent live strain of Salmonella typhimurium}; Ivanoff B et al.; Before determining the quantity of mouse intestinal secretory IgA after oral vaccination, we have tried to find the best conditions of immunization with an avirulent S . typhimurium strain given by oral route . The results show the superiority of the live vaccin with respect to the heat-killed one.

Mol Gen Genet, 1974, 135(4), 339 - 48
Inhibition of DNA synthesis and cell division in Salmonella typhimurium by azide; Ciesla Z et al.; Evidence has been obtained that sodium azide is an inhibitor of cell division in wild-type and aziA strains of Salmonella typhimurium . The bacteria grown in media containing sodium azide and glucose formed long filaments . It has been found that sodium azide had a stronger inhibitory effect on DNA synthesis than on cell mass increase . When filaments produced by azide action were transferred to azide-free medium very rapid increase in DNA content was observed during the first 45 min . After this time, when relative DNA content was increased the rate of DNA synthesis was reduced and cell divisions reappeared . Inhibitory effect of azide on DNA biosynthesis in vitro was observed with toluenized cells of S typhimurium . Only ATP-dependent radioactive dTMP incorporation into DNA was affected by sodium azide . It had no effect on the incorporation in the absence of ATP . Mutant aziC was isolated in S . typhimurium by scoring for clones with normal cell division in the presence of sodium azide . Azide had much less effect on DNA biosynthesis in vivo and in vitro in aziC cells as compared with isogenic controls.

Mol Gen Genet, 1974, 135(2), 123 - 30
Estimation of the D period from residual division after exposure of exponential phase bacteria to chloramphenicol; Kubitschek HE; Values of the D period, between termination of chromosome replication and cell division, were determined from measurements of residual cell division after exposure of exponential phase cultures of Escherichia coli B/r and K12 and of Salmonella typhimurium to chloramphenicol . The results obtained by this method were compared with earlier results for E . coli B/r obtained from measurements of DNA content per cell and were found to be almost identical . For each, values of the D period were independent of growth rate, and the average value of D-26.1 plus or minus 1.2 min obtained by residual division is in good agreement with the value of 25 min obtained earlier . These results indicate that the method of residual division provides a good measure of the duration of the D period . Values of D were also independent of growth rate for each of the other strains.

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