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J Clin Oncol, 1990 Aug, 8(8), 1408 - 18
Phase II trial of Serratia marcescens extract in recurrent malignant astrocytoma; Jaeckle KA et al.; Nineteen assessable patients with recurrent malignant astrocytomas who had failed standard therapy (surgery, radiation, and/or chemotherapy) were treated on a phase I-II trial with a biologic extract of Serratia marcescens (ImuVert; Cell Technology, Boulder, CO) a new biologic response modifier (BRM) . Two complete responses (CRs) were seen, of 63 and 77+ weeks duration . One minor response (MR) occurred, of 6 weeks duration . There were four additional stable (S) patients, with durations of 58+, 39, 12, and 7 weeks . Median time to progression and median survival in the CR plus MR patients were 63 and 129+ weeks, respectively . Overall, median time to progression and median survival were 12 and 19 weeks, respectively . Three patients are alive greater than or equal to 2.5 years from study entry . Common toxicities included transient (less than 72 hours) tenderness, induration, and erythema at the injection sites . Systemic toxicities were less frequent and included fever, chills, nausea/vomiting, headache, arthralgia, and hypotension . The response rate (CR plus MR) to this new BRM is modest (16%) . However, the observation of CRs in patients with advanced recurrent malignant astrocytomas, with acceptable overall toxicity, warrants further study of this agent.

J Bacteriol, 1990 Aug, 172(8), 4322 - 8
Differentiation of Serratia marcescens 274 into swimmer and swarmer cells; Alberti L et al.; We describe a new sensory response in the enteric bacterium Serratia marcescens . When grown in liquid media, the bacteria were short rods with one to two flagella and displayed classical swimming behavior . Upon transfer to a solid surface (0.7 to 0.8T% agar medium), the bacteria underwent a dramatic change of form . They ceased septation, elongated, and expressed numerous (10 to 100) flagella that covered the lateral sides of the cells . The bacteria now displayed a different form of locomotion--swarming--which allowed them to rapidly move over the top of the solid surface . The differentiation to either swimmer or swarmer cells could be reversed by growth on solid or liquid medium, respectively . To identify conditions that influence this differentiation, the growth environment of S . marcescens was manipulated extensively . The swarming response was monitored by visual and microscopic observation of cell movement on solid surfaces, by immunofluorescent labeling followed by microscopic observation for the presence of elongated, profusely flagellated cells, as well as by estimation of induction of flagellin protein, using Western immunoblot analysis . Conditions that imposed a physical constraint on bacterial movement, such as solid or viscous media, were the most efficient at inducing the swarming response . No chemical constituent of the medium that might contribute to the response could be identified, although the existence of such a component cannot be ruled out . Both swimmer and swarmer cells had flagellin proteins of identical molecular weight, which produced similar proteolysis patterns upon digestion with trypsin.

Mol Gen Genet, 1990 Jul, 222(2-3), 446 - 51
The metalloprotease gene of Serratia marcescens strain SM6; Braunagel SC et al.; Utilizing the DNA sequence of the metalloprotease from Serratia strain E-15, we isolated and sequenced the homologous gene from Serratia strain SM6 . These two genes are similar at both the DNA and protein sequence level . Expression of the protease gene in Escherichia coli was achieved by use of the lac promoter . This resulted in the production and excretion of an immunologically detectable but inactive protein of slightly higher molecular weight than that from Serratia . We introduced the cloned gene into previously described protease mutants . The observed pattern of protease expression suggested that these mutations fall into three classes.

J Bacteriol, 1990 Jul, 172(7), 3932 - 9
Co-overproduction and localization of the Escherichia coli motility proteins motA and motB; Wilson ML et al.; The motility genes motA and motB of Escherichia coli were placed under control of the Serratia marcescens trp promoter . After induction with beta-indoleacrylic acid, the levels of MotA and MotB rose over about a 3-h period, reaching plateau levels approximately 50-fold higher than wild-type levels . Both overproduced proteins inserted into the cytoplasmic membrane . Growth and motility were essentially normal, suggesting that although the motor is a proton-conducting device, MotA and MotB together do not constitute a major proton leak . Derivative plasmids which maintained an intact version of motB but had the motA coding region deleted in various ways were constructed . With these, the levels of MotB were much lower, reaching a peak within 30 min after induction and declining thereafter; pulse-chase measurements indicated that a contributing factor was MotB degradation . The low levels of MotB occurred even with an in-frame internal deletion of motA, whose translational initiation and termination sites were intact, suggesting that it is the MotA protein, rather than the process of MotA synthesis, that is important for MotB stability . Termination at the usual site of overlap with the start of motB (ATGA) was not an absolute requirement for MotB synthesis but did result in higher rates of synthesis than when translation of motA information terminated prematurely . Even in the total absence of MotA, the MotB that was synthesized was found exclusively in the cytoplasmic membrane fraction . In wild-type cells, MotA was estimated by immunoprecipitation to be in about fourfold excess over MotB; a previous estimate of 600 +/- 250 copies of MotA per cell then yielded an estimate of 150 +/- 70 copies of MotB per cell.

J Med Microbiol, 1990 Jul, 32(3), 211 - 4
Conditions required for the bactericidal activity of 4-quinolones against Serratia marcescens; Lewin CS et al.; The conditions required to kill Serratia marcescens with nalidixic acid, ciprofloxacin, norfloxacin or ofloxacin were determined in nutrient broth and in phosphate-buffered saline . They were found to be similar to the conditions required for these 4-quinolones to kill Escherichia coli . Bacterial RNA synthesis and bacterial cell division were essential for the bactericidal activity of nalidixic acid but all three fluoroquinolones were bactericidal against non-dividing S . marcescens . However, as with E . coli, bacterial RNA synthesis was essential for the bactericidal activity of norfloxacin though this was not required to kill S . marcescens with ciprofloxacin or ofloxacin.

FEMS Microbiol Lett, 1990 Jun 15, 58(1), 23 - 8
Antibacterial activity of phosphono dipeptides based on 1-amino-1-methylethanephosphonic acid; Zboinska E et al.; Phosphono dipeptides containing 1-amino-1-methylethanephosphonic acid (phosphonic acid analogue of alpha-methylalanine, MeAlaP) and glycine, alanine, valine, leucine phenylalanine, proline, methionine or lysine as N- terminal component were synthesized in order to determine their antibacterial properties . Peptides containing alanine, leucine, valine phenylalanine and methionine showed marked in vitro activity, especially against Escherichia coli and Serratia marcescens strains . There were, however, generally less potent than the respective phosphono dipeptides based on 1-aminoethanephosphonic acid (phosphonic acid analogue of alanine, AlaP) . The possible mechanism of action of the peptides of MeAlaP involves their active transport into the bacterial cell, followed by intracellular release of MeAlaP, which most likely inhibits alanine racemase, a key enzyme in peptidoglycan biosynthesis . Studies on the uptake of AlaMeAlaP and LeuMeAlaP by Escherichia coli mutants defective in the oligopeptide permease suggest that these peptides are not transported by the oligopeptide transport system.

FEMS Microbiol Lett, 1990 Jun 15, 58(1), 115 - 8
A major outer membrane protein of Serratia marcescens which was easily solubilized and had a capacity to bind to calcium; Tada Y et al.; Easily solubilized major outer membrane protein was found in Serratia marcescens . The protein was originally obtained as a membrane-associated, insoluble protein in the outer membrane when the cells were slightly disrupted . However, the amount of this protein in the outer membrane gradually decreased with the time of sonication . The decrease was not due to decomposition of the protein but to solubilization into a soluble fraction after a long period of disruption . The molecular weight of this protein was 47 kDa and it bound calcium . Another 40 kDa calcium binding protein was also found in the outer membrane of S . marcescens.

J Bacteriol, 1990 Jun, 172(6), 3015 - 22
Surface-active novel glycolipid and linked 3-hydroxy fatty acids produced by Serratia rubidaea; Matsuyama T et al.; A Serratia rubidaea isolate with wetting activity when grown at 30 but not 37 degrees C was examined for the production of specific lipids . Two novel lipids (rubiwettins R1 and RG1) were isolated and shown to be able to lower the surface tension of saline to 26 mN/m . These lipids were located in extracellular vesicles found in a 30 degrees C culture of S . rubidaea . Chemical structures of these biosurfactants were determined by degradation product analyses, infrared spectroscopy, mass spectrometry, and proton nuclear magnetic resonance spectroscopy . Rubiwettin R1 was proposed to be a mixture of 3-(3'-hydroxytetradecanoyloxy)decanoate, 3-(3'-hydroxyhexadecenoyloxy)decanoate, and minor molecular isomers . The structure of rubiwettin RG1 was proposed to be beta-D-glucopyranosyl 3-(3'-hydroxytetradecanoyloxy)decanoate . The importance of such surface-active exolipids in bacterial occupancy on surfaces was suggested.

Yakugaku Zasshi, 1990 Jun, 110(6), 414 - 25
{Studies on resistant mechanisms in the resistant bacteria to chlorhexidine . II . Chemical components of the cell membrane and the electron microscopical observation of cell surface structure of chlorhexidine-resistant bacteria}; Ohta S; The mechanisms of resistance of Serratia marcescens and Pseudomonas cepacia to chlorhexidine were studied . Leakage of the cellular component such as protein was observed in a chlorhexidine sensitive strain (S1) of S . marcescens when S1 was treated with chlorhexidine at 40 micrograms/ml concentration, while this phenomenon was not observed in a resistant strain (R1) . The following observations were made concerning about cell surface structure in the chlorhexidine sensitive and resistant strains of S . marcescens by chemical analyses of membrane components and electron microscopical studies of the thin sections of the cells . (1) When the S1 strains was treated with chlorhexidine, the outer membrane of the cells formed a wrinkled surface with irregular blebs, and some of which broke out to form various sizes of granules . The R1 strain did not undergo such morphological changes under the same conditions used in the sensitive strain . (2) A prominent protein with apparent molecular weight of 45 K was found exclusively in the R1 strain of S . marcescens as major outer membrane protein, while it was not found in S1 strain . (3) There were no differences in the composition of phospholipids and the amount of 3-hydroxytetradecanoic acid between S1 and R1 strains of S . marcescens . In Pseudomonas cepacia PCJ1 which is resistant to chlorhexidine, 50 K protein was also observed as a major protein of outer membrane of the cells . In contrast to the strain, a mutant of the strain, #102 which was obtained from PCJ1 strain by the treatment with methanesulfonic acid ethylester, did not possess the 50 K protein in its outer membrane . These data suggested that outer membrane components of bacteria were related importantly in resistant mechanism.

FEMS Microbiol Lett, 1990 Jun 1, 57(3), 255 - 8
The effect of nuclease on transformation efficiency in Serratia marcescens; Palomar J et al.; No differences in the efficiency of transformation were observed from both plasmid and chromosomal DNA in Serratia marcescens 2170 and an extracellular nuclease defective isogenic strain . The efficiency of transformation was the same for Escherichia coli 5K and E . coli containing a recombinant plasmid conferring the ability to synthesize a S . marcescens nuclease . From these results we conclude that the extracellular nuclease of S . marcescens 2170 is not the main cause of the low efficiency of transformation observed in this bacterium.

Appl Environ Microbiol, 1990 Jun, 56(6), 1833 - 8
Fermentation studies of the secretion of Serratia marcescens nuclease by Escherichia coli; Biedermann K et al.; The secretion of a Serratia marcescens nuclease was followed by fermentation with Escherichia coli . A plasmid, p403-SD2, carrying a 1.3-kilobase-pair insert with a 0.4-kilobase-pair region upstream of the nuclease gene caused a growth-phase-regulated expression of nuclease in E . coli in the same way as that seen in S . marcescens . Deletion of the regulatory gene generating plasmid p403-Rsa1 resulted in a constitutive expression of the nuclease . Anaerobiosis stimulated the expression from p403-SD2 in stationary growth phase by a factor of 10 compared with expression stimulated by cultivation in aerobic conditions; no such effect was found for plasmid p403-Rsa1 . Different nutritional factors caused the expression level and the amount of extracellular nuclease to vary more when nuclease was expressed from plasmid p403-SD2 than when it was expressed from plasmid p403-Rsa1 . A correlation between the regulatory gene and the extracellular secretion of nuclease is proposed.

Blood, 1990 May 15, 75(10), 1989 - 90
PPACK-thrombin inhibits thrombin-induced platelet aggregation and cytoplasmic acidification but does not inhibit platelet shape change; Greco NJ et al.; We have re-evaluated the previously reported ability of TLCK-thrombin (N alpha-tosyl-L-lysine chloromethyl ketone-treated alpha-thrombin) and PPACK-thrombin (D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone-treated alpha-thrombin) to inhibit alpha-thrombin-induced platelet activation (Harmon JT, Jamieson GA: J Biol Chem 261:15928, 1986; and Harmon JT, Jamieson GA: Biochemistry 27:2151, 1988) . Despite several cycles of derivatization with TLCK (10,000-fold molar excess), preparations of TLCK-thrombin have been found to contain about 4% residual alpha-thrombin activity, suggesting that these preparations are an equilibrium mixture of TLCK-thrombin and alpha-thrombin and cannot be used for evaluating competition between these two agents . In contrast, alpha-thrombin activity was completely inhibited by PPACK at 15-fold molar excess . PPACK-thrombin, free of unreacted PPACK and devoid of residual alpha-thrombin activity, did not markedly affect platelet shape change at concentrations as high as 1 mumol/L, but inhibited aggregation and secretion in intact platelets activated with the minimal concentration of alpha-thrombin causing a full response (0.3 to 0.5 nmol/L) and yielded a 50% inhibition constant (IC50) for inhibition of aggregation by PPACK-thrombin of 110 nmol/L . This inhibition was specific for alpha-thrombin-induced platelet activation, and no inhibition was seen with activation induced by ADP, collagen, epinephrine, ristocetin, or arachidonate . At these low alpha-thrombin concentrations (approximately 0.4 nmol/L), a persistent cytoplasmic acidification was observed of -0.062 +/- 0.016 pH units, although alkalinization was observed at higher alpha-thrombin concentrations (greater than 1 nmol/L) . While inhibition of aggregation and secretion occurred when alpha-thrombin and PPACK-thrombin were added simultaneously, inhibition of cytoplasmic acidification and of the elevation of cytoplasmic {Ca2+} induced by low concentrations of alpha-thrombin (0.4 nmol/L) occurred only if platelets were preincubated with PPACK-thrombin for 5 minutes before the addition of alpha-thrombin . In platelets treated with Serratia marcescens protease to remove glycoprotein lb (GPlb), alpha-thrombin-induced shape change was attenuated but persisted in the presence of a high concentration (2 mumol/L) of PPACK-thrombin, although aggregation and secretion were inhibited, as seen in intact platelets . The IC50 value for inhibition of aggregation by PPACK-thrombin was approximately 1 mumol/L at the higher alpha-thrombin concentrations (5 nmol/L) required for full activation in this case . These results suggest that PPACK-thrombin may be a useful probe of platelet function since it specifically blocks platelet aggregation and secretion induced by alpha-thrombin.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimicrob Agents Chemother, 1990 May, 34(5), 755 - 8
Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates; Yang YJ et al.; Reexamination of Serratia marcescens isolates obtained in 1982 revealed two organisms that were resistant to the penem FCE 22101 (MIC, 512 micrograms/ml) and imipenem (MIC, 16 micrograms/ml) and that had slightly reduced susceptibilities to meropenem (MIC, 0.12 micrograms/ml) . MICs of these agents for typical S . marcescens isolates were 1 to 8, 0.25 to 0.5, and 0.03 micrograms/ml, respectively . The two isolates were fully susceptible to broad-spectrum cephalosporins, and only one was highly resistant to ampicillin and carbenicillin (MICs, greater than 1,024 micrograms/ml) . Both isolates had beta-lactamases that focused at pIs 8.2 and 9.7 . The penicillin-resistant isolate additionally produced the TEM-1 enzyme . The enzymes with pIs of 8.2 and 9.7 were separated by cation-exchange chromatography . The pI 8.2 beta-lactamase was a class I enzyme of the type found in most S . marcescens isolates . It was almost inactive against carbapenems and penems, as was the class I enzyme from another S . marcescens strain . The pI 9.7 enzyme hydrolyzed penems and carbapenems rapidly: kcat (turnover number) values for FCE 22101, imipenem, and meropenem were 3.4, 26, and 1% of the kcat value for cephaloridine, respectively; kcat/Km values were 140, 915, and 150% of the kcat/Km value for cephaloridine, respectively . Otherwise, the pI 9.7 enzyme had predominantly penicillinase activity . It was inhibited more readily by clavulanate than by tazobactam and was inactivated by the chelating agents EDTA and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid . Expression of the pI 9.7 enzyme was not associated with any plasmid, and production was not transferred to Escherichia coli K-12 recipients, even after the mobilizing plasmid pUZ8 was inserted into the S . marcecens donor strains.

Infect Immun, 1990 May, 58(5), 1247 - 53
Outer membrane and porin characteristics of Serratia marcescens grown in vitro and in rat intraperitoneal diffusion chambers; Malouin F et al.; The composition and antibiotic permeability barrier of the outer membrane of Serratia marcescens were assessed in cells grown in vivo and in vitro . Intraperitoneal diffusion chambers implanted in rats were used for the in vivo cultivation of bacteria . Outer membranes isolated from log-phase bacterial cells recovered from these chambers were compared with membranes isolated from cells grown in vitro . Analysis revealed that the suspected 41-kilodalton porin and the OmpA protein were recovered on sodium dodecyl sulfate-polyacrylamide gels in equal quantities . Several high-molecular-weight proteins, thought to be iron starvation induced, appeared in the diffusion chamber-grown cells . The outer membrane permeability barriers to cephaloridine were similar in in vivo- and in vitro-grown cells based on permeability coefficient calculations . The permeability coefficient of cephaloridine in S . marcescens cells (30.3 x 10(-5) to 38.9 x 10(-5) cm s-1) was greater than that obtained for an Escherichia coli strain expressing only porin OmpC but smaller than those obtained for the E . coli wild type and a strain expressing only porin OmpF . Functional characterization of the suspected porin was performed by using the planar lipid bilayer technology . The sodium dodecyl sulfate-0.4 M NaCl-soluble porin from both in vitro- and in vivo-grown cells showed an average single-channel conductance in 1 M KCl of 1.6 . A partial amino acid sequence (19 residues) was obtained for the S . marcescens porin . The sequence showed a very high homology to the E . coli OmpC porin . These data identified the S . marcescens outer membrane 41-kilodalton protein as a porin by both functional and amino acid analyses . Also, the methodology used allowed for efficient growth and recovery of diffusion chamber-grown bacterial cells and permitted identification of specific in vivo-induced changes in bacterial cell membrane composition.

J Hosp Infect, 1990 May, 15(4), 323 - 37
Hygienic hand disinfection: a comparative study with chlorhexidine detergents and soap; Nicoletti G et al.; The efficacy of two chlorhexidine hand-wash detergents and liquid soap was compared in a laboratory trial using artificial contamination of fingers with Micrococcus and Serratia . Agents were assessed for both a rapid and sustained effect after a single contact, and for a cumulative persistent effect after multiple contact over four days . Disinfectant activities were compared by statistical analysis of log reduction factors and log count time gradients (decimal reduction times) . The latter analysis attempted to accommodate significant subject variation in response to both agent and organism . All handwashing methods significantly reduced contamination levels . Both chlorhexidine formulations were significantly better than soap in their activity against Micrococcus, but were not more effective than soap in removing contamination with Serratia . Both chlorhexidine preparations showed significant skin persistence and were generally acceptable to subjects after prolonged use . Some effect of the formulation of the hand-wash on chlorhexidine activity was demonstrated.

Infect Immun, 1990 May, 58(5), 1269 - 72
Inactivation of chemotactic activity of C5a by the serratial 56-kilodalton protease; Oda T et al.; The effects of the 56-kilodalton protease (56K protease) from Serratia marcescens on complement-derived chemotactic activity were examined . Fresh human serum was incubated with zymosan to produce C5a . This activated serum was then incubated with various concentrations of 56K protease, and the chemotactic activity of mouse peritoneal exudate polymorphonuclear leukocytes (PMN) and macrophages was evaluated . A significant dose-dependent decrease of chemotactic activity was observed after protease treatment . Furthermore, treatment of human recombinant C5a with 56K protease at a dose of 1.0 microgram/ml resulted in a complete loss of chemotactic activity . When the living bacteria of the virulent strain, which produced about 10 times more protease than did the less virulent strain, were injected intraperitoneally into mice, the magnitude of infiltration of polymorphonuclear leukocytes into the peritoneal cavity was much lower than that caused by the less virulent strain . Because complement-dependent chemotactic activity is an initial response to bacterial infection, these results suggest indirect pathogenic functions of serratial proteases that suppress chemotactic activity.

J Biol Chem, 1990 Apr 15, 265(11), 6055 - 60
The RNA antiterminator causes transcription pausing in the leader region of the tryptophan operon; Roesser JR et al.; In vitro transcription studies with a trp leader DNA template derived from a double deletion mutant of Serratia marcescens revealed that the transcription complex pauses synthesis of part of the RNA antiterminator, structure 2:3 . Pausing was enhanced by NusA protein and was dependent on the concentration of UTP in the transcription reaction mixture . A weak antiterminator pause also was detected during transcription of the wild-type S . marcescens trp leader template in the presence of NusA protein and 1 microM UTP . Transcription pausing following synthesis of the antiterminator also was observed in a cell-free transcription-translation system . Antiterminator-induced pausing may play an important role in vivo by delaying synthesis of RNA segment 4 . This delay may influence basal level control in cells with an excess of tryptophan . In addition, formation of the antiterminator pause structure may introduce a more stringent tryptophan starvation requirement for RNA polymerase to read through the attenuator.

J Chemother, 1990 Apr, 2(2), 79 - 81
In-vitro susceptibility of clinical isolates of Serratia species to antimicrobial agents; Sofianou D et al.; The in-vitro activities of 12 antimicrobial agents against a total of 80 clinical isolates of Serratia marcescens and Serratia liquefaciens were determined by a broth microdilution method . Ampicillin and cefazolin were totally inactive against these organisms . The other beta-lactam antibiotics such as piperacillin, cefotaxime, ceftazidime, and the aminoglycosides such as gentamicin, tobramycin and netilmicin showed poor or moderate activity against Serratia isolates . Aztreonam and amikacin inhibited most of the strains tested . Imipenem and ciprofloxacin were very active in inhibiting all strains . Within the genus, S . liquefaciens was more resistant to aztreonam, ceftazidime and amikacin than S . marcescens.

J Biol Response Mod, 1990 Apr, 9(2), 194 - 204
The effect of a bacterial vaccine on tumors and the immune response of ICR/Ha mice; Havas HF et al.; This study examined the effect of mixed bacterial vaccine (MBV), a biological response modifier prepared from Streptococcus pyogenes and Serratia marcescens, on the immune system of mice and on the regression of a transplantable mouse tumor sarcoma 37 . The study examined MBV's biological properties and analyzed its chemical composition . The chemical composition varied with the growth media . A typical centrifuged, dialyzed supernate of the serum-containing preparation was found to consist mainly of protein and minimal amounts of carbohydrate and endotoxin, while MBV made with synthetic medium contained similar amounts of all three . MBV was nontoxic for mice, which gained weight following the injection of 0.5-1.0 ml of MBV . MBV caused regression of 20-100% of well-established mouse tumors without appreciable toxicity . MBV also had a striking effect on the immune response of mice to sheep red blood cells . When administered simultaneously with antigen injection, MBV increased the number of antibody-secreting splenocytes measured by the plaque-forming assay threefold . Serum antibody levels also increased two- to threefold . MBV did not enhance the immune response to pneumococcal polysaccharide type III, a B-cell-dependent response . However, the in vivo administration of MBV increased the in vitro response to MBV and the B-cell mitogen lipopolysaccharide . MBV compares favorably with other biological response modifiers because of its enhancing effect on the immune response and its oncolytic properties at nontoxic levels.

J Am Vet Med Assoc, 1990 Apr 1, 196(7), 1102 - 5
Serratia marcescens mastitis in a dairy herd; Wilson DJ et al.; Serratia marcescens caused clinical mastitis in 5 cows and nonclinical mastitis in 21 cows of a 190-cow herd . Repeated bacteriologic culture of specimens from the cows, postmilking teat dip, environment, and equipment was performed . Serratia marcescens was not isolated from the dip, environment, or equipment . Progress of the infection in cows was monitored for 10 months . Some cows remained infected with S marcescens for at least 10 months . Economic loss estimates were based on Dairy Herd Improvement Association linear score reports . The average nonclinical loss was about $22/cow.

Microbiologica, 1990 Apr, 13(2), 157 - 9
Stability of conjugative and non-conjugative R-plasmids from Serratia marcescens to gyrase inhibitors; Llanes C et al.; The stability of conjugative and non-conjugative R-plasmids was compared using two gyrase inhibitors (novobiocin and ciprofloxacin) . Conjugative R-plasmids from eighteen ticarcillin resistant Serratia marcescens were more stable than non-conjugative R-plasmids from eleven ticarcillin resistant bacteria of the same species . Moreover, novobiocin (gyrase B sub-unit inhibitor) is a better curing agent than ciprofloxacin (A sub-unit inhibitor).

Int J Artif Organs, 1990 Apr, 13(4), 205 - 10
Detection of endotoxin antibody in long-term dialysis patients; Yamagami S et al.; Endotoxins are often seen in dialysate . They are derived from Gram-negative bacteria especially Pseudomonas, E . coli and Serratia . Endotoxins are large-molecular-weight substances with an average molecular weight of 10(8) . These large units can be divided into subunits down to a molecular weight of 10,000 which are thought to pass through dialyzer membranes . To investigate this, endotoxin antibody levels were measured in two groups of patients on chronic regular hemodialysis, a low-flux group using cellulosic membrane dialyzers (cuprophan and cuproammonium rayon (CAR) and a high-flux group using synthetic polymer membrane dialyzers (PMMA, EVAL) . Using an ELISA based on standard endotoxin antibodies the percentages of patients in the low flux group with endotoxin antibodies were 26.9% with Cuprophan and 25% with CAR, not significantly different from a normal control group . In the PMMA and EVAL groups, it was 53.6% and 68.4% respectively . Back filtration of dialysate into blood is understood as the main reason for the entry of endotoxin in patients treated with high-flux dialyzers.

Mol Microbiol, 1990 Apr, 4(4), 651 - 5
Serratia marcescens rpr gene sensitizes Escherichia coli wild-type, xth, and nfo strains to methyl methanesulphonate; Murphy KE et al.; It is reported here that the rpr DNA repair gene of Serratia marcescens does not complement an Escherichia coli xth nfo AP endonuclease mutation for resistance to methyl methanesulphonate (MMS) . Rather, rpr sensitized Escherichia coli wild-type, xth, and nfo strains to MMS . Also, it was found that rpr could not complement a triple tag alkA recA mutation in E . coli, indicating that there are limits to rpr complementing capabilities . It was determined that rpr gene dosage was not a factor in recA complementation . MMS sensitization of an E . coli wild-type strain, however, was directly related to rpr copy number . These data indicate that Rpr does not have an associated AP endonuclease activity, and that it is incapable of substituting for Tag I, Tag II, and RecA in a tag alkA recA background.

J Am Vet Med Assoc, 1990 Mar 15, 196(6), 890 - 3
In vitro and in vivo evaluation of a 0.5% chlorhexidine gluconate teat dip; Boddie RL et al.; The activity of a 0.5% chlorhexidine gluconate postmilking teat germicide in reducing the numbers of Staphylococcus aureus and Streptococcus agalactiae on the skin of excised teats from cows was determined . The product yielded logarithmic reductions of 4.09 and 4.10 against S aureus and Str agalactiae, respectively, compared with 3.80 and 3.81 reductions, using a 1% iodophor dip . Germicide tolerance to an organic load containing Serratia marcescens or Pseudomonas spp was also determined . Organisms were not recovered from the product 8 hours after introduction of a simulated organic load containing either species of bacteria . The germicide was further evaluated against S aureus and Str agalactiae, using experimental challenge-exposure procedures in a research dairy herd . Efficacy was 73.4% (P less than 0.001) against S aureus and 68.1% (P less than 0.005) against Str agalactiae.

J Dairy Sci, 1990 Mar, 73(3), 621 - 6
Characteristics of biological aerosols in dairy processing plants; Kang YJ et al.; The viable aerosol in dairy processing plant environments was characterized by using an Andersen six-stage sieve sampler and a Reuter centrifugal sampler . Artificially introduced Serratia marcescens were detected in the air during drain flooding and after rinsing the floor with a pressured water hose, thus illustrating the ability of a specific microorganism to be disseminated from drains and wet surfaces via physical disruption activities often observed in food plants . Once a high concentration of wet viable aerosol was generated, it took 40 or more min to return to the background level in the absence of forced ventilation or other activity . The greatest reduction in viable particles occurred during the first 10 min . Estimated mean aerosol particle sizes were decreased from approximately 4.6 to 3.2 mu with time lapse . The estimated mean aerosol particle sizes from actual dairy processing plant environments ranged from approximately 4.3 to 5.3 mu . In addition, a more heavily contaminated dairy processing environment contained larger aerosol particles . These results indicate that the RCS sampler will often overestimate the true aerosol concentration in highly contaminated air, because mean particle sizes are over 4 mu in diameter.

Diagn Microbiol Infect Dis, 1990 Mar-Apr, 13(2), 93 - 7
Serum bactericidal activity from intravenous ciprofloxacin and azlocillin given alone and in combination to healthy subjects; Orlando PL et al.; Ciprofloxacin plus azlocillin have been shown to exhibit in vitro synergy versus a variety of organisms, including Pseudomonas aeruginosa . This study examined this interaction in vivo, testing serum bactericidal activity (SBA) in six healthy male subjects after intravenous administration of ciprofloxacin 4 mg/kg (C), azlocillin 60 mg/kg (A), and the two simultaneously (C/A) . Eight different organisms were tested: four isolates of P . aeruginosa with varying susceptibilities to C and A, and one isolate each of Escherichia coli (EC), Staphylococcus aureus (SA) Serratia marcescens (SM), and Klebsiella pneumoniae (KP), all of which were susceptible to both drugs . Blood samples were collected at the end of 30-min infusions and at 4 and 8 hr . Reciprocal titers were plotted versus time and area under the bactericidal titer curve (AUBC) calculated to assess antibacterial interactions . Results indicated that P . aeruginosa-1 (PA-1), EC, and KP were synergistically killed by C/A . AUBC for PA-1 were C = 36, A = 11, C/A = 144, p less than 0.05 . AUBC for EC were C = 1059, A = 180, C/A = 1504, p = 0.05 . AUBC for KP were C = 327, A = 97, C/A = 584, p = 005 . Additive effects were demonstrated versus all of the other organisms except Serratia marcescens, where an indifferent effect was observed . Ciprofloxacin plus azlocillin may be a useful combination of the treatment of selected Gram-negative bacillary infections.

Carbohydr Res, 1990 Feb 25, 196, 127 - 31
Structure of the putative O23 antigen of Serratia marcescens; Oxley D et al.; A neutral glycan containing L-rhamnose and 2-acetamido-2-deoxy-D-galactose is one of two polymers present in the lipopolysaccharide extract from the reference strain for Serratia marcescens serogroup O23 . The glycan, which has the disaccharide repeating-unit shown, shares structural features with polymers from several other O serogroups . ----4)-alpha-L-Rhap-(1----4)-beta-D-GalpNAc-(1----.

J Chromatogr, 1990 Feb 23, 525(2), 329 - 38
Column liquid chromatography of endotoxins; Somlyo B et al.; A new, fast and highly reproducible column liquid chromatographic method was elaborated for the analysis and small-scale preparative isolation of endotoxin from Serratia marcescens Bizio (ATCC No . 264) . This procedure detects contaminants of such preparations with high sensitivity and it is capable of separating them from endotoxic components . Extensive heterogeneity of both 5% trichloroacetic acid and phenol-water-extracted endotoxin preparations was recorded . Heterogeneity among the endotoxic components of purified preparations could also be detected by this method . Measurements of biological activities, such as Limulus amoebocyte lysate activation, lymphoblastogenesis (mitogenicity) and tumor necrosis factor (TNF) liberation were carried out on the chromatographically separated fractions . During these studies, non-toxic but in vitro TNF-generating components of crude endotoxin extracts were also detected.

Transfusion, 1990 Feb, 30(2), 146 - 9
Microbial challenge of a blood cell separator outside-seal bowl system; Jacobson MS et al.; The ability to store platelets beyond 24 hours requires a functionally closed system . This study tested the ability of a cell separator bowl seal system to resist penetration of microbial contamination under normal running conditions and under extreme environmental stress . Three test organisms, Micrococcus luteus, Serratia marcescens, and Staphylococcus epidermidis, were applied directly to the bowl at the edge of the seal or aerosolized and passed through the centrifuge chamber while the cell separator was run through a simulated platelet collection . A sterile, bacteriologic nutrient medium was perfused through the tubing set, thus simulating the flow of blood fractions . Following the procedure, the medium was examined for microbial growth . The concentration of aerosolized bacteria ranged from 5.2 x 10(1) to 3.9 x 10(3) colony-forming units (CFU) per mL, and the concentration of bacteria applied to the edge of the seal ranged from 1.9 x 10(5) to 2.8 x 10(9) CFU per mL . The positive control, direct inoculation of S . marcescens into the circulating medium (50 CFU/500 mL), resulted in recovery of the identical organism after 24 hours' incubation . No contamination of the system was detected in 40 experiments with aerosolized bacteria or in 32 experiments in which bacteria were applied directly to the seal . This study demonstrates that this sealed-bowl system resists microbial contamination.

J Bacteriol, 1990 Feb, 172(2), 572 - 8
Nucleotide sequences of the sfuA, sfuB, and sfuC genes of Serratia marcescens suggest a periplasmic-binding-protein-dependent iron transport mechanism; Angerer A et al.; The cloned sfu region of the Serratia marcescens chromosome confers the ability to grow on iron-limited media to an Escherichia coli K-12 strain that is unable to synthesize a siderophore . This DNA fragment was sequenced and found to contain three genes termed sfuA, sfuB, and sfuC, arranged and transcribed in that order . The sfuA gene encoded a periplasmic polypeptide with calculated molecular weights of 36,154 for the precursor and 33,490 for the mature protein . The sfuB gene product was a very hydrophobic protein with a molecular weight of 56,589 . The sfuC gene was found to encode a rather polar but membrane-bound protein with a molecular weight of 36,671 which exhibited strong homology to consensus sequences of nucleotide-binding proteins . The number, structural characteristics, and locations of the SfuABC proteins were typical of a periplasmic-binding-protein-dependent transport mechanism . How Fe3+ is solubilized and taken up across the outer membrane remains an enigma.

Infect Control Hosp Epidemiol, 1990 Feb, 11(2), 67 - 70
The effects of surfactant systems and moisturizing products on the residual activity of a chlorhexidine gluconate handwash using a pigskin substrate; Benson L et al.; A series of handwashing experiments using a pigskin substrate and Serratia marcescens as the contaminant compared the residual activity of a chlorhexidine detergent handwash product alone and in combination with anionic and nonionic-based moisturizing products and surfactant systems . The anionic based moisturizing products and the anionic surfactant system almost completely destroyed the residual antibacterial activity of the chlorhexidine, while the nonionic-based products had minimal effect.

Antibiot Khimioter, 1990 Feb, 35(2), 13 - 5
{Effect of mitomycin on the biosynthesis of extracellular endonuclease by Serratia marcescens}; Iusupova DV et al.; The effect of mitomycin C on extracellular endonuclease activity of Serratia marcescens was studied . It was shown that in a concentration of 0.02-1.0 micrograms/ml, mitomycin C markedly increased biosynthesis of the endonuclease by growing and washed cells, the cell productivity being increased 80-100 times . The highest increase in the cell productivity was observed when mitomycin C was added to the cells at the end of the growth exponential phase . The increase in the activity of the extracellular endonuclease was due to the de novo synthesis of the enzyme since it was inhibited by chloramphenicol.

J Hosp Infect, 1990 Feb, 15(2), 167 - 72
Nosocomial Serratia marcescens individualized by five typing methods in a regional hospital; Larose P et al.; The relationships between 69 isolates obtained from 26 patients who were affected by two Serratia marcescens hospital outbreaks occurring in the urology and postnatal wards, were examined by five typing methods for epidemiological purposes . Serotyping, antibiotic resistance profile and electrophoretic analysis of enzymes identified three groups of isolates, while biotyping and bacteriocin typing identified only two . These surveys allowed us to demonstrate the existence of independent episodes of cross-infection among patients of each ward.

J Clin Microbiol, 1990 Jan, 28(1), 55 - 8
Use of molecular typing to study the epidemiology of Serratia marcescens; McGeer A et al.; Although Serratia marcescens is a well-known nosocomial pathogen, investigation of its hospital ecology has been limited by the lack of available typing techniques . During an investigation of the occurrence of this organism in a neonatal intensive care unit, we evaluated a number of such techniques . Using a selective medium, we conducted prospective surveillance of neonatal rectal colonization and environmental contamination with S . marcescens . In 8 months of surveillance, 5.1% (20 of 394) of the infants admitted to the unit became colonized . Most sink surfaces and drains were also culture positive . Differences between isolates could not be detected in biotypes from a commercial identification system (MicroScan) or by antibiograms, total protein fingerprints, or plasmid profiles . Serogrouping and genomic DNA restriction endonuclease analysis revealed the presence of six strains that colonized infants and a similar number of environmental strains . These two methods were concordant, with the exception that genomic DNA analysis demonstrated lack of relatedness between some strains within the same serogroup . DNA restriction endonuclease analysis was practical and reliable . The differences this method detected between environmental and neonatal strains provided strong evidence that the environment was not an important reservoir for S . marcescens in our neonatal intensive care unit.

J Clin Microbiol, 1990 Jan, 28(1), 20 - 6
Immunophysical characterization of human isolates of Serratia marcescens; Hamadeh RM et al.; The immunophysical characteristics of 29 Serratia marcescens strains isolated from hospitalized patients in three different cities were studied . Their outer membrane antigens were compared by solid-phase radioimmunoassay inhibition, and their proteinase K-treated, whole-cell lysates were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis . The strains had a limited number of unique outer membrane lipopolysaccharide (LPS) and capsular polysaccharide (K) antigens . By solid-phase radioimmunoassay inhibition, these strains could be divided into four distinct LPS and five K antigenic groups . By SDS-PAGE, the LPS groups could be further divided into three distinct SDS-PAGE core polysaccharide profiles and five distinct O-side-chain polysaccharide profiles . Immunoblot analysis with rabbit antiserum confirmed the limited heterogeneity of these isolates . Of the strains tested, no PAGE profile was unique to blood or nonblood isolates or to organisms collected from a given hospital . Variability of O and core PAGE profiles was not a function of organism growth cycle . Five representative Serratia strains were tested by SDS-PAGE and immunoblot analysis and in a bactericidal assay with normal human serum . We found that (i) the normal human serum had antibodies to the LPS of each of the strains, (ii) the anti-LPS antibody measured by immunoblot did not correlate with the level of bactericidal activity in the normal human serum, (iii) three of four sepsis isolates were serum sensitive, (iv) two Serratia strains serum sensitive in log-phase growth became serum resistant in late stationary-phase growth and under limiting nutrient conditions, and (v) no LPS PAGE profile distinguished serum-sensitive from serum-resistant strains.

J Clin Microbiol, 1990 Jan, 28(1), 136 - 9
Numerical analysis of electrophoretic periplasmic protein patterns, a possible marker system for epidemiologic studies; Gargallo-Viola D et al.; The whole-cell and periplasmic protein (PP) compositions of 22 Serratia marcescens isolates were examined . Numerical analysis of whole-cell protein patterns was not a useful procedure for measuring relationships between organisms at the subspecific level . However, there was a very good correlation between electrophoretic PP pattern results and those obtained previously from multilocus enzyme electrophoresis (electrophoretic type) and biotype (D . Gargallo-Viola, J . Clin . Microbiol . 27:860-868, 1989) . Clustering of isolates by using PP patterns compared by coefficients based on peak position (Dice coefficient) gave more precise information than that obtained by correlation coefficients . PP patterns appeared to be a useful tool that may be of value for epidemiologic studies.

Cornea, 1990, 9 Suppl 1, S44 - 6; discussion S47
Is your office safe? No; Farris RL; The practitioner's office can be an unsafe environment for fitting contact lens (CLs), owing to numerous reservoirs of microbial contamination . These include sinks, trial lenses, solutions, lens cases, multidose dropper bottles, and storage trays . Microbes may also be introduced to the eyes via the practitioner's fingers, the patient's lashes or lids, or cosmetic residues on the ocular adnexa . Because sterility is difficult to achieve in an office, CL fitters must accept the more realistic goal of disinfection . Periodic cultures are necessary to monitor the effectiveness of office hygiene and disinfection . Cultures are especially important, considering that the panel of organisms routinely used to test lens care solutions may not reflect those in office settings, which may become resistant to preservatives . It has been shown, for example, that 50% of chlorhexidine-preserved solutions used in offices can become contaminated with Serratia marcescens within 7 days of bottle opening . At present, it appears that contamination is best avoided by using solutions containing 15 ppm of polyaminopropylbiguanide (PAPB) . Frequent replacement of solutions, trial lenses, and lens cases may also help to reduce the likelihood of microbial contamination in the office.

Genetika, 1990 Jan, 26(1), 5 - 11
{Comparative analysis of the structure and function of recA genes from Serratia marcescens Sb and Escherichia coli K-12}; Bakhlanova IV et al.; Nucleotide sequence of the 1276 bp fragment of Serratia marcescens DNA coding for the recASM gene has been determined . This structure was shown to contain an ORF corresponding to a protein with molecular weight of 37766 D . Comparative analysis of the regulatory part of recASM and recAEC (Escherichia coli) demonstrated identity of "-35" and "-10" boxes for these genes and similarity of the SOS box and the enhancer sequences . A comparison of the amino acids sequences of RecASM, RecAEC and RecAPA (Pseudomonas aeruginosa) proteins revealed a great conservatism in the N-terminus and in some structural patches (alpha-helices and beta-sheets) of the RecA proteins predicted by the model of Blanar et al . In contrast, a strong variability of the C-terminus (for the last 25 amino acids, in particular) was revealed . A necessity for definite amino acids composition of the carboxy-terminal end is discussed.

Adv Exp Med Biol, 1990, 256, 525 - 35
Immunoadjuvanticity of endotoxins and nontoxic derivatives for normal and leukemic immunocytes; Friedman H et al.; Studies with FLV infected mice, a model for retrovirus induced acquired immunodeficiency, showed that intact lipopolysaccharide rich extract from Serratia marcescens as well as the nontoxic polysaccharide derivative free of lipid A were equally adjuvantic in enhancing antibody formation to sheep erythrocytes, both in vivo and in vitro . The PS-rich endotoxin derivative had little or no toxic activity in leukemic animals as occurred with intact endotoxin . The adjuvanticity of both the nontoxic polysaccharide derivative as well as the intact endotoxin in enhancing antibody formation in FLV infected mice was evident also in vitro when spleen cells from infected animals were immunized with sheep erythrocytes simultaneously with the polysaccharide in comparison with the LPS . Supernatants from normal spleen cells treated in vitro either with the polysaccharide or the intact endotoxin showed immunoenhancing helper activity for both normal and FLV infected spleen cells and this enhancing activity was due to IL-1 induced by either bacterial product . Thus the immunoenhancing soluble mediator, i.e., IL-1, is induced equally by PS or LPS and has immunorestorative activity for FLV infected animals . The potential value of the nontoxic PS as an immunoadjuvant in retrovirus immunosuppressed lymphoid cells is evident . The results of these studies suggest that further investigations concerning the nature and mechanism involved in such adjuvancticity is warranted.

Mol Microbiol, 1990 Jan, 4(1), 119 - 22
Processes of genome evolution reflected by base frequency differences among Serratia marcescens genes; Sharp PM; The G + C content of silent sites in codons varies greatly among Serratia marcescens genes; the value in any one gene seems to reflect a balance between mutation pressure towards high G + C content and natural selection constraining choice among synonymous codons . Interestingly, non-coding sequences have substantially lower G + C content than silent sites thought to be under little selective constraint.

Infection, 1990 Jan-Feb, 18(1), 29 - 30
Haematogenous Serratia marcescens endophthalmitis in an HIV-infected intravenous drug addict; Alvarez R et al.; A case of haematogenous Serratia marcescens endophthalmitis in an HIV-infected intravenous drug addict is described . The patient was admitted with fever, ocular pain and visual loss in the right eye following an i.v . injection of pulverized buprenorphine . A vitreous humor culture grew S . marcescens . The patient was treated with i.v . ceftriaxone (2 g b . i . d.), i.v . amikacin (500 mg b . i . d.) and p . o . fosfomycin (1 g q . i . d.) for three weeks . The ocular infection was cured, although the visual function was lost, leading to blindness . To our knowledge, this is the second case in the reviewed Anglo Saxon literature of S . marcescens endophthalmitis in parenteral drug addicts.

Microbios, 1990, 63(256-257), 151 - 7
Growth depression of Serratia marcescens by plasmids that belong to incompatibility group P; Platt DJ et al.; The IncP plasmids R702, RP4 and derivative plasmids including RP4::Mu cts were studied in two pigmented strains of Serratia marcescens . Maintenance of these plasmids resulted in reduced pigmentation and the growth rate of colonies was slower than the plasmid-free parent organisms . DNA inserts and deletions in RP4 altered both the pigmentation phenotype and growth rate of S . marcescens transconjugants and was inversely related to the change in molecular weight . The unrelated plasmids R446b and R46, although of comparable size to RP4, produced neither effect and Rts1, more than three times larger than RP4, produced no visible change in pigmentation phenotype and only a minimal decrease in growth rate . Integration of RP4::Mu cts into the Serratia genome restored pigmentation and growth rate to the same level as the plasmid-free parent . Partial induction at 43 degrees C restored the plasmid to a cytoplasmic state in a proportion of surviving colonies which were typically pale and slow growing.

J Bacteriol, 1990 Jan, 172(1), 342 - 9
Expression of Serratia marcescens extracellular proteins requires recA; Ball TK et al.; A previously described regulatory mutation which abolishes expression of the extracellular nuclease of Serratia marcescens is shown to be a mutation of the Serratia recA gene . The defect in nuclease expression could be restored by introducing a plasmid carrying the recA gene of Escherichia coli . The DNA sequence of the Serratia gene is very similar to that of the E . coli gene . The putative LexA-binding site of the Serratia recA gene is almost identical to that of E . coli, along with the promoter . A similar LexA-binding site can also be found upstream of the nuclease gene . As expected from this finding, we show that nuclease expression can be induced by SOS-inducing agents such as mitomycin C . Although inducible in S . marcescens, the nuclease was expressed only at the uninduced levels in E . coli and could not be induced by mitomycin C . The extracellular chitinase and lipase were similarly affected by the mutations altering nuclease expression and were also induced by mitomycin C.

Int J Immunopharmacol, 1990, 12(6), 589 - 98
ImuVert activation of natural killer cytotoxicity and interferon gamma production via CD16 triggering; Cunningham-Rundles S et al.; The effect and mechanism of action of ImuVert, a new biological response modifier consisting of ribosomes and natural membrane vesicles of Serratia marcescens, on endogenous natural killer (NK) cells and activated NK activity has been analyzed . The studies showed that endogenous NK activity of peripheral blood mononuclear cells (PBMC) from normal cell donors was significantly increased (P less than 0.03) against K562, U937, and Molt-4 target cells . PBMC from cord blood of newborn infants lacking NK activity were upregulated (1.5-4 fold over endogenous NK activity) by ImuVert . Other studies showed that the abnormal NK activity of PBMC from patients with the human immunodeficiency virus (HIV) infection was significantly augmented in vitro (P less than 0.01) by ImuVert . ImuVert strongly stimulated interferon gamma production and in combination with interleukin 2 produced synergistically enhanced interferon gamma production and greater cytotoxicity than that induced by either alone . Studies on lymphocyte differentiation antigen expression following treatment with ImuVert indicated that ImuVert triggers interferon gamma production through binding the low affinity IgG Fc receptor, type III, CD16 . The studies suggest that ImuVert may trigger interferon gamma production by binding to the Fc receptor and that the amplitude of the ensuing reaction and the ability of ImuVert to induce cytotoxicity in a setting where this activity has been down regulated is based on the absence of suppressor activation or direct contra suppressor activity.

Scand J Infect Dis Suppl, 1990, 74, 129 - 32
The postantibiotic effect of amikacin alone and in combination with piperacillin on gram-negative bacteria; Isaksson B et al.; The in vitro postantibiotic effect (PAE) of amikacin was investigated using a bioluminescent assay of bacterial ATP . Two strains each of Escherichia coli, Pseudomonas aeruginosa and Serratia marcescens were exposed for one hour to different concentrations of amikacin . The aminoglycoside was removed by a 10(-3) dilution and regrowth of bacteria was followed at hourly intervals by monitoring bacterial ATP . The length of the PAE was concentration-dependent and was approximately four to six hours for the three strains at amikacin concentrations normally reached in serum during standard dosing . The PAE of amikacin in combination with 32 mg/l piperacillin on Ps . aeruginosa was also studied . These cultures were incubated with piperacillin for one hour . Thereafter different concentrations of amikacin 0.5-64 mg/l were added and the incubation then continued with the combinations for one more hour . The PAEs produced by the drugs in combination were longer than the sum of the individual effects of the drugs when they were used alone . Knowledge of synergistic PAE could have clinical implications for optimal dosing schedules during combination antimicrobial chemotherapy.

Microbiol Immunol, 1990, 34(4), 347 - 54
Inverse relationship between the flagella formation and prodigiosin synthesis in Serratia marcescens; Kobayashi N et al.; Treatment by polymyxin B sulfate and ethylenediaminetetraacetate separated a 40 kilodalton (kDa) protein from the nonpigmented Serratia marcescens and even from the nonpigmented bacteria of the pigmented strains, whereas the same treatment separated the 100 kDa protein associated with the pigment formation from the pigmented bacteria . Lysozyme treatment separated the 100 kDa and/or 40 kDa proteins correlated with the pigmented level . The 40 kDa protein was not an outer membrane protein but a flagellin . These results suggest that the flagella formation was inversely related with the pigment formation.

Chemotherapy, 1990, 36(2), 109 - 16
In vivo evaluation of a dual-action antibacterial, Ro 23-9424, compared to cefotaxime and fleroxacin; Beskid G et al.; The dual-action antibacterial R 23-9424 (desacetylcefotaxime linked to the quinolone fleroxacin) is a new antibacterial agent with excellent in vitro activity . It was evaluated for in vivo efficacy in comparison with the cephalosporin cefotaxime and the quinolone component, fleroxacin . Ro 23-9424 demonstrated significant activity against all strains tested in systemic infections, including those strains resistant in vivo to cefotaxime (Staphylococcus aureus 753, Serratia marcescens SM and Pseudomonas aeruginosa 8780) and fleroxacin (Streptococcus pneumoniae 6301 and Streptococcus pyogenes . In prophylactic studies, Ro 23-9424 compared favorably with fleroxacin against Escherichia coli and with cefotaxime against S . pyogenes, but Ro 23-9424 was considerably more active than cefotaxime against E . coli and more active than fleroxacin against S . pyogenes . In a murine pneumonia model, Ro 23-9424 was equivalent in activity to cefotaxime against S . pneumoniae and more active than cefotaxime against Klebsiella pneumoniae . Fleroxacin was inactive against S . pneumoniae and about 20-fold more active than Ro 23-9424 against K . pneumoniae . In a murine meningitis infection caused by S . pneumoniae, Ro 23-9424 was 3 times as active as cefotaxime, while fleroxacin was inactive . When meningitis was induced by K . pneumoniae, Ro 23-9424 was as active as the quinolone, while cefotaxime was inactive . In a neutropenic (immunocompromised) model, Ro 23-9424 was more active than cefotaxime against P . aeruginosa and 5-fold less active than fleroxacin . In the control normal (immunocompetent) mouse infection, Ro 23-9424 was 3-fold more active than cefotaxime, but 10-fold less active than fleroxacin.

EMBO J, 1990 Jan, 9(1), 217 - 24
The cecropin locus in Drosophila; a compact gene cluster involved in the response to infection; Kylsten P et al.; Cecropins are antibacterial peptides that are synthesized in insects as a response to infection . As a first step towards a molecular study of the induction of this response, we have isolated genomic clones that cover the cecropin locus in Drosophila melanogaster . This locus was found to be unique, and it was mapped cytologically to the chromosomal location 99E . Sequence analysis showed it to be unusually compact, with three expressed genes and two pseudogenes within less than 4 kb of DNA, and with another homologous region less than 4 kb away . Two of the genes, A1 and A2, encode a product that is identical to the major cecropin from Sarcophaga peregrina, while the cecropin encoded by the B gene differs in five positions . Cecropin transcripts appear within an hour after bacteria have been injected into the hemocoel, reach a maximum after 2-6 h, and have almost disappeared again after 24 h . The B gene is induced in parallel with the A genes, but on a lower level . The cecropin genes were also induced when the flies were kept on food with the Drosophila pathogenic bacterium Serratia marcescens Db10 or its non-pathogenic derivative Db1140.

Lens Eye Toxic Res, 1990, 7(3-4), 677 - 83
Nontoxic concentration of ceftazidime and flomoxef sodium for intravitreal use--evaluated by in-vitro ERG; Tanabe J et al.; The effects of ceftazidime (CAZ) and flomoxef sodium (FMOX) on the in-vitro electroretinogram (ERG) of albino rabbits were studied . The a-wave, the b-wave and the oscillatory potential (OP) were unchanged by 0.3mM (0.19mg/ml) CAZ-containing solution . The OP was suppressed by 0.5mM (0.32mg/ml) CAZ . The a-wave, the b-wave and the OP were unchanged by 0.5mM (0.26mg/ml) FMOX . The OP was suppressed and its peak latency was delayed by 2mM (0.52mg/ml) FMOX . The concentration of 0.3mM (0.19mg/ml) CAZ was higher than its minimum inhibitory concentration (MIC) against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Serratia marcescens and Propionibacterium acnes . The concentration of 0.5mM (0.26mg/ml) FMOX was higher than its MIC against Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens and Propionibacterium acnes.

Urol Res, 1990, 18(5), 299 - 303
Increased renal scarring by bacteria with mannose-sensitive pili; Matsumoto T et al.; Renal scars are thought to be the end stage of chronic pyelonephritis and one of the most important causes of renal insufficiency and renal hypertension . The role of bacterial pili was examined in scar formation after an infection of newly constructed bacterial strains using the recombinant DNA technique, which possessed either mannose resistant (MR) or mannose sensitive (MS) pili of Serratia marcescens . Strains that differed in only a single virulence factor, namely, MR or MS pili, were used in a rat model of chronic pyelonephritis . In this model, MS-piliated bacteria stimulated renal scarring more severely than non-piliated or MR-piliated bacteria.

Nephron, 1990, 56(2), 130 - 5
Suitability of colchicine and superoxide dismutase for the suppression of renal scarring following an infection with bacteria showing mannose-sensitive pili; Matsumoto T et al.; Two new strains of Serratia marcescens were constructed by the gene manipulation method from the clinical isolate US 46, which has two kinds of pili--mannose-sensitive (MS) and mannose-resistant (MR) ones--on the cell surface . After cloning the genes of the MS and MR pili, either the MS or the MR gene was transferred to the nonpiliated Escherichia coli, and MS- or MR-piliated strains were obtained . In the experimental pyelonephritis model of rats, MS- or MR-piliated bacteria were inoculated directly to the renal parenchyma, and the following results were obtained . MS-piliated rather than MR-piliated strains stimulated severe scarring of the kidney, and this scarring was suppressed by treatment with colchicine or superoxide dismutase (SOD) during an early stage of the infection . These findings suggest that MS-piliated bacteria stimulated polymorphonuclear leukocytes, which released large amounts of superoxide resulting in renal scarring . SOD was hoped to be a drug capable of preventing renal scarring, and such a result was successfully obtained.

Microbiol Immunol, 1990, 34(9), 765 - 73
Protective effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) against various microbial infections in neutropenic mice; Matsumoto M et al.; Protective effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on microbial infections was studied in cyclophosphamide (CPA)-induced neutropenic mice . The neutropenic mice showed severely decreased resistance against systemic infections of Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Staphylococcus aureus, and Candida albicans . When such mice were injected subcutaneously with rG-CSF on four consecutive days beginning the day after CPA injection, the decreased anti-microbial resistance of the mice was restored to the level of that in normal mice . The anti-infective effect of rG-CSF was dose-dependent and the 50% effective doses (ED50) in various microbial infections tested were 1-10 micrograms/kg/day . The results suggest that rG-CSF is useful for protection of neutropenic patients from microbial infections.

Carbohydr Res, 1989 Dec 21, 195(1), 117 - 22
Structure of the O-specific galactan from the lipopolysaccharide of the reference strain for Serratia marcescens serogroup O24; Oxley D et al.; The putative O-specific polysaccharide for Serratia marcescens serogroup O24 is a galactan with a branched, trisaccharide repeating-unit of the structure shown . The structure of the backbone is identical to that of the linear galactans isolated from the reference strains for S . marcescens serogroups O16 and O20, presumably accounting for the serological cross-reactions observed . (Formula: see text)

Carbohydr Res, 1989 Dec 21, 195(1), 111 - 5
Structure of a neutral polymer isolated from the lipopolysaccharide of the reference strain for Serratia marcescens serogroup O18; Oxley D et al.; A neutral polymer (the putative O antigen) has been isolated from the lipopolysaccharide of the reference strain for Serratia marcescens serogroup 018 . From the results of spectroscopic and degradative studies, the repeating unit of the polymer was identified as a linear tetrasaccharide having the structure shown . ----2)-alpha-L-Rhap-(1----2)-alpha-L-Rhap-(1----6)-alpha-D- GlcpNAc-(1----

Cancer Res, 1989 Dec 15, 49(24 Pt 1), 7093 - 7
Effects on growth and energy metabolism in untransformed and transformed BALB/c mouse fibroblasts by a novel cytotoxic compound; Keler T et al.; A lipid, recently discovered as a contaminant of endotoxin and White-Type polysaccharide preparations from an unidentified isolate of Serratia marcescens, was named DCX for its direct cytotoxic activity . Previously we have shown that DCX is cytotoxic to several transplantable tumors and transformed cell lines in culture at nanomolar concentrations, while normal fibroblasts were significantly more resistant . In this study the selectivity and mechanism of DCX-mediated cytotoxicity was examined more thoroughly with the use of clonally related cell lines . DCX is growth inhibitory but is not cytotoxic to a BALB/c embryonal cell line . Transformation by Simian Virus 40 renders a cloned derivative cell line sensitive to the cytotoxicity of DCX . Treatment of both cell lines with DCX increased 2-deoxyglucose uptake and lactate production, and decreased ATP levels . Electron micrographs show extensive damage to mitochondria in cells treated with DCX . The results indicate that the growth inhibitory activity of DCX in these cells is due to effects on mitochondria resulting in depletion of cellular ATP . The data suggest that the basis for selective cytotoxicity is in how the different cells are able to cope with lower energy levels.

Clin Chim Acta, 1989 Dec 15, 185(3), 357 - 67
Pathogenic potentials of bacterial proteases; Maeda H et al.; Six separate molecular mechanisms for pathogenesis attributed to bacterial proteases are described . (I) . Enhancements of vascular permeability and edema formation which result from the activation of kinin generating cascade such as Hageman factor by the proteases . (II) . Degradation of defense oriented proteins including IgG and IgA as well as destruction of structural matrices such as fibronectin, proteoglycan and collagen . (III) . Inactivation of complement system and generated chemotactic factor from C3 and C5 . (IV) . Degradation of regulatory plasma protease inhibitors (serpins) including alpha 1-protease inhibitor, alpha 2-macroglobulin (alpha 2M), C1-esterase inhibitor, alpha 2-antiplasmin and antithrombin-III . (V) . The protease forms a transitory stable enzyme/inhibitor(alpha 2M) complex . It binds to and internalizes into the cells which possess alpha 2M-receptor such as fibroblasts via the alpha 2M-receptor, and the protease activity is regenerated in cells, and subsequently intracellular integrity is destroyed resulting in cell killing . (VI) . The serratial 56 kDa (56K) protease is found to potential viral yield 100 fold more when influenza virus infected mice were subjected to administrations of this protease intranasally . This results in rapid and much elevated lethality.

Nucleic Acids Res, 1989 Dec 11, 17(23), 9783 - 96
Cloning, characterization and heterologous expression of the SmaI restriction-modification system; Heidmann S et al.; The genes coding for the class-II Serratia marcescens restriction-modification system have been cloned and expressed in E . coli . Recombinant clones, restricted incoming phage only poorly; the recombinant plasmids, however, became fully modified in vivo, i.e . completely resistant against digestion with R.SmaI . The determined nucleotide sequence of the cloned system revealed three open reading frames with lengths of 252 bp, 741 bp, and 876 bp . Through various deletion experiments and an insertion-mutation experiment the 876 bp open reading frame could be assigned to the SmaI DNA modification enzyme and the 741 bp open reading frame to the SmaI restriction endonuclease . Mapping of the transcription start sites of the genes revealed that the SmaI endonuclease is transcribed as polycistronic mRNA together with a 252 bp long preceding open reading frame of unknown function . No homology was found when comparing the amino acid sequence of M.SmaI with the published sequences of m5C-specific DNA modification methyltransferases . On the other hand, a stretch of 14 amino acids in the C-proximal region of M.SmaI shows a significant homology to the C-proximal amino acid sequences of the N6A-methyltransferases M.HinfI and M.DpnIIA and the N4C-methyltransferase M.PvuII.

J Gen Microbiol, 1989 Dec, 135 ( Pt 12), 3319 - 27
Cloning of the Serratia marcescens recA gene and construction of a Serratia marcescens recA mutant; Liao CL et al.; A recombinant plasmid, pSM2513, containing an 8.5 kb DNA insert was isolated from a genomic library of Serratia marcescens by using interspecific complementation . This plasmid conferred resistance to methyl methanesulphonate and UV irradiation upon recA mutants of Escherichia coli and enhanced recombination proficiency, as measured by Hfr-mediated conjugation, in recA mutants of E . coli . Furthermore, when recA mutants of E . coli harbouring pSM2513 were subjected to UV irradiation, filamentation of the cells was observed . This did not occur upon UV irradiation of the same mutants harbouring the cloning vector alone . These results imply that the S . marcescens recA gene on pSM2513 is functionally similar to the E . coli recA gene in several respects . Restriction enzyme analysis and subcloning studies revealed that the S . marcescens recA gene was located on a 2.7 kb Bg/II-KpnI fragment of pSM2513, and its gene product of approximately 39 kDa resembled the E . coli RecA protein in molecular mass . Using transformation-mediated marker rescue, a recA mutant of S . marcescens was successfully constructed; its proficiency both in homologous recombination and in DNA repair was abolished compared with its parent.

J Bacteriol, 1989 Dec, 171(12), 6566 - 72
Characterization of the precursor of Serratia marcescens serine protease and COOH-terminal processing of the precursor during its excretion through the outer membrane of Escherichia coli; Miyazaki H et al.; The Serratia marcescens serine protease, which is directed by the gene encoding a precursor composed of a typical NH2-terminal signal sequence, a mature enzyme domain, and a large COOH-terminal domain, was excreted through the outer membrane of Escherichia coli . The precursor, with the expected molecular size (110 kilodaltons), was detected in an insoluble form in the periplasmic space of E . coli cells after induction with isopropyl-beta-D-thiogalactopyranoside of the expression of the gene under the control of the tac promoter . Upon membrane fractionation of the disrupted cells by sucrose density gradient centrifugation, the precursor was recovered from a fraction slightly heavier than the outer membrane fraction but not from the inner membrane fraction . Conversion of the precursor into the mature form, which was accompanied by its excretion into the medium, was observed even in the absence of de novo protein synthesis caused by the addition of chloramphenicol . The mutated gene product lacking all of the COOH-terminal domain was localized in the periplasmic space only and was not excreted into the medium . Additional mutant genes were generated by site-directed mutagenesis to test the role of some amino acids in the excretion of this protease in E . coli . The mutant protein with no protease activity because of the change of the catalytic residue Ser-341 to Thr was still excreted into the medium but with abnormal processing . Both self-processing and host-dependent processing of the precursor seem to be involved in the excretion of the mature enzyme . Replacement of the four Cys residues, two in the mature enzyme and two in the COOH-terminal domain, with Ser in different combinations caused a distinct or complete loss of excretion, suggesting that a certain conformation possibly formed via disulfide bonding was important for the excretion of the S . marcescens protease.

J Bacteriol, 1989 Dec, 171(12), 6629 - 36
A cryptic fimbrial gene in Serratia marcescens; Moriya T et al.; The gene coding for the mannose-sensitive hemagglutinating fimbriae in Serratia marcescens US5 was cloned into Escherichia coli K4 with a cosmid vector system . One of the transformants, US5-1, expressed two morphologically distinct fimbriae, one that was 5-nm wide and one that was 3-nm wide . The latter fimbria was morphologically and serologically indistinguishable from that of strain US5 . Genetic analysis of transformant US5-1 showed that the gene responsible for the 5-nm-wide fimbriae was located more than 10 kilobases away from the gene responsible for the 3-nm-wide fimbriae . The molecular sizes of the subunits of these two fimbriae, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were 19 kilodaltons for the 3-nm-wide fimbriae and 20 kilodaltons for the 5-nm-wide fimbriae . Serologically, the 5-nm-wide fimbriae did not cross-react with monoclonal or polyclonal antibodies raised against the mannose-sensitive hemagglutinating fimbriae of strain US5 . Strain EL101, which expressed only the 5-nm-wide fimbriae, did not agglutinate chicken or human erythrocytes . These experimental results suggest that the gene for the 5-nm-wide fimbriae is cryptic in strain US5 and is expressed in E . coli K4 only after it is moved by transformation.

J Gen Microbiol, 1989 Dec, 135 ( Pt 12), 3289 - 302
Streptomyces griseus streptomycin phosphotransferase: expression of its gene in Escherichia coli and sequence homology with other antibiotic phosphotransferases and with eukaryotic protein kinases; Lim CK et al.; The aphD gene of Streptomyces griseus, encoding a streptomycin 6-phosphotransferase (SPH), was sub-cloned in the pBR322-based expression vector pRK9 (which contains the Serratia marcescens trp promoter) with selection for expression of streptomycin resistance in Escherichia coli . Two hybrid plasmids, pCKL631 and pCKL711, were isolated which conferred resistance . Both contained a approximately 2 kbp fragment already suspected to include aphD . The properties of in vitro deletion derivatives of these plasmids were consistent with the presumed location of aphD . In vitro deletion of a sequence including most of the trp promoter largely, but not quite completely, abolished the ability of the plasmid to confer streptomycin resistance, confirming that expression was indeed principally from the trp promoter . A polypeptide of approximately 34.5 kDa was present in minicells containing plasmids that conferred streptomycin resistance, but was absent when the plasmids contained in vitro deletions removing streptomycin resistance . Part of the fragment was sequenced and an open reading frame corresponding to aphD identified . A computer-assisted comparison of the deduced SPH sequence with those of other antibiotic phosphotransferases suggested a common structure A-B-C-D-E, where B and D were conserved between all sequences compared while A, C and E divided between the streptomycin and hygromycin B phosphotransferases on one hand and kanamycin/neomycin ones on the other . A composite sequence data base was searched for homologues to consensus matrices constructed from five approximately 12-residue subsequences within blocks B and D . For one subsequence, corresponding to the N-terminal portion of block D, those sequences from the database that yielded the highest homology scores comprised almost entirely either antibiotic phosphotransferases or eukaryotic protein kinases . Possible evolutionary implications of this homology, previously described by other groups, are discussed.

Zhonghua Wai Ke Za Zhi, 1989 Dec, 27(12), 750 - 2, 781-2
{Opportunistic infection and systemic dissemination in burns}; Zhang YP; A total of 303 strains of opportunistic bacteria were isolated from our burned patients during April, 1980 to December, 1987 . Among which Pseudomonas aeruginosa accounted for 161 strains (54.1%), Serratia accounted for 56 strains (18.5%), just the two species accounted for 72.6% in total . Among twenty commonly used antibiotics, Amikacin and Polymyxin-B were comparatively sensitive . Further reviewing the drug sensitivity of the two species, we found the sensitivity rates were variable among the strains isolated from different sources . To Polymyxin-B, strains isolated from wound surfaces were of 86.1% and 90.7% respectively, from subeschar tissues or visceral organs were of 53.8% and 39.3%, from blood stream were of 44.4% and 40% . It seemed that the drug resistance of the invading organisms was stronger than that of surface ones . It suggested that the Pseudomonas aeruginosa and Serratia play an important role in infection of burned patients.

J Clin Microbiol, 1989 Dec, 27(12), 2702 - 5
Improved O-serotyping method for Serratia marcescens; Gaston MA et al.; In a previous study, we found that some O serotypes of Serratia marcescens, as defined by agglutination tests, were not based on lipopolysaccharide (LPS) O antigens . We developed a dot enzyme immunoassay with a high degree of LPS specificity and tested 104 distinct clinical strains . Only 7 of the 24 existing O antigens were found in more than one strain: O12/O14 (30.8% of strains examined), O21 (12.5%), O8 (8.7%), O6/O7 (5.8%), O4 (3.8%), O18 (2.9%), and O9 (2.9%) . Two new antigens, S1254 (13.5%) and S3255 (3.8%), were also found . Agglutination tests with O antisera identified the LPS antigen in only 36 strains . Prodigiosin production was restricted to serotypes O8, O6, and S3255 and strains with a rough or semirough LPS phenotype . Dot immunoassay appears to offer greater accuracy than agglutination tests for serotype identification in S . marcescens.

J Clin Microbiol, 1989 Dec, 27(12), 2697 - 701
O-antigen specificities of the serotype strains of Serratia marcescens; Gaston MA et al.; O antigens of the 24 O-serotype strains of Serratia marcescens were investigated in dot enzyme immunoassay with whole-cell antigens and by immunoblotting with lipopolysaccharide (LPS) antigens . Three pairs of strains, O2/O3, O6/O7, and O12/O14, had indistinguishable LPS antigens, despite having distinct specificities in agglutination tests with whole-cell antigens . Strong cross-reactions were also found in LPS antigens from strains O9/O15, O17/O19, O10/O22, and O16/O20 . No high-molecular-weight LPS corresponding to O-side-chain material was detected in strain O11 or O13 . A panel of absorbed antisera was prepared to facilitate the detection of a reduced set of LPS antigens in a dot enzyme immunoassay . We conclude that there are discrepancies between the existing serotypes as defined by agglutination tests and the antigenic composition of LPS antigens extracted from the serotype strains and that surface antigens other than LPS make a major contribution to the definition of serotype in the species.

Biull Eksp Biol Med, 1989 Nov, 108(11), 591 - 3
{Lowering of bactericidal activity of mouse peritoneal macrophages under combined use of staphylococcal enterotoxin type A and endotoxin}; Riabichenko EV et al.; The present study investigated the effect of staphylococcal enterotoxin type A (SEA) and endotoxin Serratia marcescens (LPS) on the phagocytosis and killing of Staphylococcus aureus by mouse peritoneal macrophages . Two hours after enterotoxin intraperitoneal injection phagocytic and bactericidal activity were depressed . 24 hours later there was increased functional activity of macrophages by SEA and LPS, apart . But when two toxins were administered together (LPS four hours later enterotoxin) marked inhibition of bacterial killing was observed . When peritoneal macrophages were treated in vitro for 24 hours with the same toxins they were also markedly suppressed in bactericidal activity.

Hinyokika Kiyo, 1989 Nov, 35(11), 1951 - 4
{Infectious cysts of a müllerian duct: a case report}; Cho M et al.; We report a case of infectious cysts of Mullerian duct . A 48-year-old male patient was referred to our department complaining of terminal miction pain on July 19, 1985 . The excretory urogram showed right lateral displacement of bladder and pelvic CT-scan demonstrated a large mass containing multiple cysts . A total of 5 percutaneous punctures was performed, but without success . The cysts were removed completely on November 26, 1985 . A large volume of pus subsequently yielded a pure culture of Serratia marcescens and multilobular cysts were observed in the incised tumor . Wound healing was delayed because of severe infection . We discussed the difficulty of the management for infectious cysts of the Mullerian duct.

Can J Microbiol, 1989 Nov, 35(11), 1037 - 42
Brown pigmentation in Serratia marcescens cultures associated with tyrosine metabolism; Trias J et al.; Serratia marcescens produced a brown pigment when grown in minimal medium in the presence of tyrosine and high concentrations of copper(II) ion . The pigment was not related to the melanin pigments, but was similar to the pigment produced by autooxidation and polymerization of 3,4-dihydroxyphenylacetate, which is synthesized in S . marcescens from tyrosine through the 3,4-dihydroxyphenylacetate catabolic pathway . The enzymes of this pathway were induced under pigment production conditions; however, 3,4-dihydroxyphenylacetate 2,3-dioxygenase remained at low activity levels, permitting the accumulation and excretion of the substrate . Mutants unable to use tyrosine as a sole carbon and energy source were able to produce brown pigments only if the step blocked by the mutation was after the synthesis of 3,4-dihydroxyphenylacetate . The ability to produce brown pigments was common to all the S . marcescens strains tested.

Rev Infect Dis, 1989 Nov-Dec, 11(6), 912 - 20
Serratia bacteremia: review of 118 cases; Saito H et al.; A review was conducted of 118 episodes of serratia bacteremia in cancer patients during a 16-year period . The infection occurred most commonly in patients with acute leukemia . Most patients acquired the infection in the hospital, and 61% had received antibiotic therapy during the preceding 10 days . Fever occurred in 90% of cases and shock in 18% . Thirty-eight percent of patients had concomitant pneumonia . Patients with shock, pneumonia, or hemorrhage had a substantially poorer prognosis . The response rate was 75% for patients who received appropriate antibiotics, 22% for those who received inappropriate antibiotics, and 29% for those who received no antibiotics . Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor diagnosis . Patients who received only an aminoglycoside had the poorest response rate among those who received appropriate therapy.

FEMS Microbiol Lett, 1989 Oct 15, 52(3), 243 - 6
Fractal spreading growth of Serratia marcescens which produces surface active exolipids; Matsuyama T et al.; An irregular fiord-like outline of a S . marcescens colony expanding on a hard agar medium was shown to be fractal which promised an extremely long array of outermost cells . For the analysis of such spreading growth, mutants defective in production of surface active exolipids (serawettin W1 and W3) and flagella-less mutants were isolated . The fractal spreading growth was found to be correlated with serrawettin production . Furthermore, serrawettin-less mutants demonstrated spreading growth when purified serrawettin W1 or W3 were supplied exogenously.

Presse Med, 1989 Oct 11, 18(32), 1569 - 71
{In vitro comparative bactericidal effect of cefotaxime and cefixime in a kinetic model}; Rolin O et al.; The bactericidal activity of cefotaxime against Escherichia coli, Klebsiella pneumoniae and Serratia marcescens, was compared with that of cefixime in an in vitro model simulating the human pharmacokinetics of these antibiotics . Kinetic parameters in this model were T1/2 = 1.3 h and Cmax = 45 mg/l for cefotaxime; T1/2 = 3.5 h and Cmax = 5 or 3.5 mg/l for cefixime . These parameters mimicked those obtained after a 1 g intravenous infusion of cefotaxime and an oral uptake of 0.4 or 0.2 g of cefixime, respectively . Both antibiotics demonstrated a strong bactericidal activity . Against Escherichia coli, the bactericidal effect of cefotaxime was slightly more rapid and more prolonged than that of cefixime: -5 log10 CFU/ml over 4 h vs -3 log10 CFU/ml over 8 h respectively . Against Klebsiella pneumoniae and Serratia marcescens, both drugs exhibited similar bactericidal activity despite different dosages and routes of administration: -2 to -3 log10 CFU/ml over 4 h.

J Biol Chem, 1989 Oct 5, 264(28), 16629 - 37
Comparison of the aspartate transcarbamoylases from Serratia marcescens and Escherichia coli; Beck D et al.; The aspartate transcarbamoylases (ATCase, EC 2.1.3.2) of Escherichia coli and Serratia marcescens have similar dodecameric enzyme structures (2(c3):3(r2} but differ in both regulatory and catalytic characteristics . The catalytic cistrons (pyrB) of the ATCases from E . coli and S . marcescens encode polypeptides of 311 and 306 amino acids, respectively; there is a 76% identity between the DNA sequences and an overall amino acid homology of 88% (38 differences) . The regulatory cistrons (pyrI) of these ATCases encode polypeptides of 153 and 154 amino acids, respectively, and there is a 75% identity between the DNA sequences and an overall amino acid homology of 77% (36 differences) . In both species, the two genes are arranged as a bicistronic operon, with pyrB promoter proximal . A comparison of the deduced amino acid sequences reveals that the active site and the allosteric binding sites, as well as most of the intrasubunit interactions and intersubunit associations, are conserved in the E . coli and the S . marcescens enzymes; however, there are specific differences which undoubtedly contribute to the catalytic and regulatory differences between the enzymes of the two species . These differences include residues that have been implicated in the T-R transition, c1:r1 interface interactions, and the CTP binding site . A hybrid ATCase assembled in vivo with catalytic subunits from E . coli and regulatory subunits from S . marcescens has a 6 mM requirement for aspartate at half-maximal saturation, similar to the 5.5 mM aspartate requirement of the native E . coli holoenzyme at half-maximal saturation . However, the heterotropic response of this hybrid enzyme is characteristic of the heterotropic response of the native S . marcescens holoenzyme: ATP activation and CTP activation . Activation by both allosteric effectors indicates that the heterotropic response of this hybrid holoenzyme (Cec:Rsm) is determined by the associated S . marcescens regulatory subunits.

Comput Appl Biosci, 1989 Oct, 5(4), 305 - 12
On the analysis of microbiological processes by Monte Carlo simulation techniques; Bermudez J et al.; The Barcelonagram is a Monte Carlo simulator recently designed in order to take account of the behaviour of living systems . In this paper we apply this technique to real bacterial growth in different and significant experimental conditions, namely (i) the growth of the Serratia marcescens in a minimal glucose-limited medium, (ii) the temperature effect on the anaerobic growth of the same strain, (iii) the growth of the Escherichia coli in a minimal medium and (iv) the normal specific growth rate of bacterial populations against the available substrate concentration . In the context of these different cases we discuss the diverse contributions of these simulated results to the understanding of the microbiological processes and the general reliability of the simulation considered as a third alternative besides both (and together with!) experience and mathematical modelling.

FEMS Microbiol Lett, 1989 Oct 1, 52(1-2), 207 - 11
Extracellular haemolytic activity of Serratia marcescens; Goluszko P et al.; Blood agar medium with dialysis membrane mounted between two layers of agar was applied to study the haemolytic activity of 28 strains of Serratia marcescens . Two kinds of lytic substances differing with their ability to pass through dialysis membrane were found . Haemolytic activity was not detected in cell-free filtrates from liquid cultures . The discrepancies between haemolytic activity in blood agar media and activity of liquid cultures were observed . Stable attachment of bacterial cells to the erythrocytes was not necessary to lysis . The possibility of extracellular haemolysin is discussed.

Scott Med J, 1989 Oct, 34(5), 525 - 8
Serratia marcescens outbreak in a paediatric oncology unit traced to contaminated chlorhexidine; McAllister TA et al.; Over an 18-month period we encountered 12 episodes of Serratia marcescens bacteraemia in 10 patients in a paediatric oncology unit . These were associated with long-term indwelling Hickman intravenous catheters (right atrial) and caused three deaths . Seven of the patients had only mild pyrexial illnesses and made a complete recovery . The source was traced to contaminated aqueous chlorhexidine in a bedside container in which plastic clamps were stored . When this was rectified the outbreak ceased . The identity of the causal Serratia strains was confirmed by plasmid analysis and they showed multiple antibiotic resistance, including the aminoglycosides . The study illustrates the emergence of S . marcescens as an opportunistic pathogen and emphasises the dangers of Hickman-associated bacteraemia.

J Clin Microbiol, 1989 Oct, 27(10), 2295 - 9
New method for determination of efficacy of health care personnel hand wash products; Mahl MC; A method of studying the effects of health care personnel hand wash products is described . The fingernail regions of the hands of volunteers are inoculated with a mixture of Escherichia coli and Serratia marcescens, and the areas are dried for a standard time . After routine hand washing, each fingernail region is individually scrubbed with an electric toothbrush which moves longitudinally to the handle into collection fluid contained in a petri dish . The test bacteria in the fluid are then enumerated . (Bacillus subtilis spores may be included as tracers to show degree of physical removal of the procedure.) This method has several advantages over the frequently used glove juice technique . Experimental designs with large numbers of volunteers, multiple sampling sites, and many hand wash products may be performed . Ten sampling sites (fingers) are available, versus the two gloved hands for testing products . (Efficiency is almost 100% in the recovery of spore tracers placed on the fingernails.) Many commercial health care personnel hand wash products containing antimicrobial agents substantive to the skin do not rapidly reduce numbers of inoculated bacteria in the fingernail regions to any greater extent than nonantimicrobial hand washes . Products containing isopropanol or ethanol are very effective in decreasing bacteria in areas around and under the fingernails.

FEMS Microbiol Lett, 1989 Oct 1, 52(1-2), 133 - 7
Plasmid-mediated resistance to fosfomycin in Staphylococcus epidermidis; Etienne J et al.; Staphylococcus epidermidis strain BM2641, isolated from a patient, was resistant to penicillin G, methicillin, aminoglycosides, chloramphenicol, macrolide, lincosamide and streptogramin B-type (MLS) antibiotics, and to high levels of fosmycin . Resistance to forsfomycin and/or to MLS was lost at low frequencies either spontaneously or after curing with novobiocin . The plasmid DNA from BM2641 and its cured derivatives was purified, analyzed by agarose gel electrophoresis and transferred to a nitrocellulose sheet . Comparative analysis of the resistance phenotypes with the plasmid content of the strains indicated that fosfomycin and MLS resistance were encoded by plasmids pIP1842 (2.5 kb) and pIP1843 (2.6 kb), respectively . Southern hybridization with a probe specific for gene fosA of Serratia marcescens showed that the fosfomycin resistance determinant in Staphylococcus is not homologous to that of Gram-negative bacteria.

J Hosp Infect, 1989 Oct, 14(3), 201 - 7
Nosocomial bacteraemia in a teaching hospital in Saudi Arabia; al-Orainey IO et al.; During a period of one year, 117 episodes of nosocomial bacteraemia were documented at King Khalid University Hospital, an incidence of 5 per 1000 admissions . Sixty-two percent were gram-negative organisms with Escherichia coli, Klebsiella spp., Serratia spp . and Pseudomonas spp . being the most frequent . Staphylococcus aureus was the most common gram-positive organism isolated . The source of infection was identified in 75% of patients . Intravenous lines accounted for a high proportion of cases (22%) . Most deaths occurred in infants and patients with serious underlying disease.

Gene, 1989 Sep 30, 81(2), 355 - 9
Multiple high-frequency transpositions of Tn5 in Serratia marcescens 274 from a thermosensitive replication mutant of plasmid R388; Estepa GR et al.; We have used the broad-host-range conjugative suicide plasmid vector described by Sasakawa and Yoshikawa {Gene 56 (1987) 283-288} for transposon mutagenesis of Serratia marcescens 274 . We report multiple transposition events of Tn5 from this vector . In addition, the unusual pattern of Tn5 transposition might provide an insight into its regulation.

J Biol Chem, 1989 Sep 25, 264(27), 16311 - 20
Subcellular location and unique secretion of the hemolysin of Serratia marcescens; Schiebel E et al.; It is shown that Serratia marcescens exports a hemolysin to the cell surface and secretes it to the extracellular space . Escherichia coli containing the cloned hemolysin genes shlA and shlB exported and secreted the S . marcescens hemolysin . A nonhemolytic secretion-incompetent precursor of the hemolysin, designated ShlA*, was synthesized in a shlB deletion mutant and accumulated in the periplasmic space of E . coli . Immunogold-labeled ultrathin sections revealed ShlA* bound to the outer face of the cytoplasmic membrane and to the inner face of the outer membrane . A number of mutants carrying 3' deletions in the shlA gene secreted truncated polypeptides, the smallest of which contained only 261 of the 1578 amino acids of the mature ShlA hemolysin, showing that the information for export to the cell surface of E . coli and secretion into the culture medium is located in the NH2-terminal segment of the hemolysin . We propose a secretion pathway in which ShlA and ShlB are exported across the cytoplasmic membrane via a signal sequence-dependent mechanism . ShlB is integrated into the outer membrane . ShlA is translocated across the outer membrane with the help of ShlB . During the latter export process or at the cell surface, ShlA acquires the hemolytically active conformation and is released to the extracellular space . The hemolysin secretion pathway appears to be different from any other secretion system hitherto reported and involves only a single specific export protein.

Infection, 1989 Sep-Oct, 17(5), 294 - 300
Nosocomial infections due to Serratia marcescens--clinical findings, antibiotic susceptibility patterns and fine typing; Bollmann R et al.; We report on nosocomial infections caused by Serratia marcescens occurring in a neonatal intensive care unit and a children's ward for cardiac intensive care . According to the plasmid pattern analysis, all isolated epidemic strains belonged to one clone . Multi-drug resistance, even to cephalosporins of the third generation and amikacin, was characteristic for all strains . Certain markers of S . marcescens (haemolysin, proteases, siderophores) which are thought to be related to virulence were studied but will require further investigation.

Rev Infect Dis, 1989 Sep-Oct, 11(5), 789 - 92
Gram-negative bacterial pyomyositis: unique case and review; Sarubbi FA et al.; Bacterial pyomyositis in tropical or temperate climates is usually associated with gram-positive organisms, and Staphylococcus aureus has been recovered most often . In contrast, skeletal muscle infection due to aerobic gram-negative bacteria is an acknowledged rarity, even in tropical areas . A literature review revealed only five organisms implicated in gram-negative pyomyositis in the United States; to this list, we add a unique case of pyomyositis caused by Serratia marcescens that occurred in a patient with multiple myeloma . Although the data are limited, it appears that lower leg muscles are more likely to be involved and that clinical cure is often achieved following appropriate drainage and antibiotic therapy.

Zentralbl Bakteriol, 1989 Sep, 271(3), 372 - 80
Automated analysis of 35-S-methionine labeled proteins by SDS-PAGE as a typing method in a suspected cluster of Serratia marcescens; Altwegg M et al.; During a nine-month period in 1986, we observed five ornithine decarboxylase-negative isolates of Serratia marcescens from four different patients . All isolates were identical in more than 50 biochemical parameters . Four isolates from three hospitalized patients were essentially identical in their susceptibility patterns to 12 antimicrobial agents . Analysis of 35-S-methionine labeled whole cell proteins by SDS-PAGE with the AMBIS system (Automated Microbiology System Inc., San Diego, CA) suggested that only three of these isolates were identical while the fourth hospital strain was more closely related to the isolate of a patient with no contact to the hospital . These results were confirmed by bacteriocin- and serotyping . We conclude that analysis of these protein patterns--which does not require special reagents - was an adequate method for typing S . marcescens.

J Bacteriol, 1989 Sep, 171(9), 5179 - 82
Evidence for unique DNA repair activity encoded by a cloned Serratia marcescens gene: suppression of Escherichia coli mutations that reduce repair of alkylated DNA; Murphy KE et al.; A recombinant plasmid containing a Serratia marcescens DNA repair gene has been analyzed biochemically and genetically in Escherichia coli mutants deficient for repair of alkylated DNA . The cloned gene suppressed sensitivity to methyl methanesulfonate of an E . coli strain deficient in 3-methyladenine DNA glycosylases I and II (i.e., E . coli tag alkA) and two different E . coli recA mutants . Attempts to suppress the methyl methanesulfonate sensitivity of the E . coli recA mutant by using the cloned E . coli tag and alkA genes were not successful . Southern blot analysis did not reveal any homology between the S . marcescens gene and various known E . coli DNA repair genes . Biochemical analysis with the S . marcescens gene showed that the encoded DNA repair protein liberated 3-methyladenine from alkylated DNA, indicating that the DNA repair molecular is an S . marcescens 3-methyladenine DNA glycosylase . The ability to suppress both types of E . coli DNA repair mutations, however, suggests that the S . marcescens gene is a unique bacterial DNA repair gene.

J Antimicrob Chemother, 1989 Sep, 24(3), 375 - 85
The pharmacokinetics and therapeutic efficacy of fleroxacin and pefloxacin in a rat abscess model; Leibovitz E et al.; The penetration, pharmacokinetics and therapeutic efficacy of fleroxacin and pefloxacin were investigated in a rat abscess model . Abscesses were induced by implanting a dialysis tube unit contaminated with Serratia marcescens in the subcutaneous tissue . Simultaneous serum, interstitial fluid (IF) and abscess fluid concentrations of the investigated antibiotics were measured 24 and 96 h after implantation . The concentrations were determined at various time intervals after the last intramuscular administration of each drug (20 mg/kg) . Peak fleroxacin and pefloxacin concentrations in the serum of the infected animals were 14.6 +/- 4.7 mg/l and 13 +/- 2.9 mg/l respectively, peak fleroxacin and pefloxacin abscess fluid concentrations after 24 h were 12.3 +/- 2.5 mg/l and 8.9 +/- 2.2 mg/l, respectively (85% and 68% of peak serum concentrations) . Abscess fluid concentrations at 96 h were: fleroxacin 4.7 +/- 2.6 mg/l and pefloxacin 4.5 +/- 1.7 mg/l . Both antimicrobials persisted significantly longer in the abscess fluid than in serum . Both drugs failed to sterilize the abscesses following a single administration; however after four consecutive administrations all abscesses became sterile . We conclude that fleroxacin and pefloxacin may be suitable for the therapy of closed space infections caused by susceptible micro-organisms.

J Gerontol, 1989 Sep, 44(5), B118 - 24
Influenza virus infection and bacterial clearance in young adult and aged mice; Wyde PR et al.; The effects of influenza A/Hong Kong/68 (H3N2) virus infection on clearance of bacteria (Staphylococcus aureus or Serratia marcescens) from lungs of young adult (8-week-old) and aged (2-year-old) CBA/2N mice were studied . No consistent differences in pulmonary bacterial clearance were observed in uninfected animals of either age group . However, both young and aged virus-infected mice consistently exhibited significantly reduced ability to clear challenge bacteria from their lungs compared to age-matched nonvirus-infected controls; this deficit was markedly more pronounced in virus-infected aged mice . The extra deficit seen in virus-infected aged animals did not correlate with pulmonary virus or interferon titers, or with severity of pulmonary histopathology . Moreover, the phagocytic and bactericidal activities of pulmonary macrophages and polymorphonuclear neutrophiles from virus-infected young and aged mice were comparable.

Gene, 1989 Aug 15, 80(2), 217 - 25
Vectors permitting visual monitoring of simple transposition events; Kozlowski M et al.; The construction and use of two novel transposon(Tn)-delivery vectors is described . These vectors carry Inc.W or Inc.N broad-host-range transfer functions cloned next to the narrow-host-range replicon of pBR329 . The host specificities of pSLX10 and pSLX23 both complement and extend the host specificities of existing Tn delivery vectors . Plasmids pSLX10 and pSLX23 were shown to transfer at high frequency in intergeneric matings . The lux genes which are present on each vector permit the visual monitoring of transconjugants which have retained a Tn element, but are devoid of plasmid molecules . pSLX10 and pLSX23 were efficiently used to generate a range of auxotrophic mutants in various strains of Pseudomonas as well as to clone genes from Serratia liquefaciens . These vectors may have general applicability to identify and clone genes in a wide range of Gram-negative bacteria.

J Gen Microbiol, 1989 Aug, 135 ( Pt 8), 2277 - 81
Putative role of a 70 kDa outer-surface protein in promoting cell-surface hydrophobicity of Serratia marcescens RZ; Bar-Ness R et al.; Serratia marcescens RZ has been previously shown to possess pronounced cell-surface hydrophobicity, as evidenced by its affinity for hydrocarbons and polystyrene . The present report suggests the involvement of a 70 kDa protein, serraphobin, in this phenomenon . The 70 kDa protein was recovered from both the cell surface and culture supernatant of hydrophobic wild-type cells, but was either totally absent or present in minor quantities in hydrophobicity-deficient mutants . Similarly, loss of hydrophobicity of RZ cells following growth at 39 degrees C was accompanied by loss of the protein . Serraphobin was capable of binding to hexadecane droplets following a brief mixing procedure, and could be desorbed by solidifying and melting the hexadecane phase.

Malays J Pathol, 1989 Aug, 11, 53 - 6
Dispersal of bacteria by an electric air hand dryer; Ngeow YF et al.; The potential risk of an electric air hand dryer contributing to airborne infection in a hospital was investigated using a strain of Serratia marcescens and a strain of coagulase-negative, streptomycin-resistant Staphylococcus . Dispersal of marker bacteria by the air dryer was demonstrated within a radius of about 3 feet from the dryer and to the investigator's laboratory coat . When paper towels were used for hand drying, no dispersal of marker bacteria was demonstrated . It is suggested that air hand dryers are unsuitable for use in critical patient care areas as they may contribute to cross infection either via airborne dissemination or via contaminated personnel.

Rev Esp Enferm Apar Dig, 1989 Aug, 76(2), 109 - 14
{The small intestine in the presence of endotoxins in the blood . Effects of splenectomy}; Lopez Muniz A et al.; We have studied the small intestine by morphologic and histochemical methods of mice treated with Serratia marcescens endotoxin (LD50); the half of the control and endotoxemic animals were splenectomized . We have not observed changes in the only splenectomized animals . We have found important alterations during the endotoxemia in the structure of small intestine, specially in the cells of the mucous membrane, as the cytoplasm and the nucleus . There are an increase of hemorrhagic phenomenons and of mucus, hemodynamic disturbances and loss of continuity of the intestinal wall . These changes are more notable in the endotoxemic and splenectomized animals than in the only endotoxemic animals . These results have be ratified by cytometric and statistic studies . The importance of the intestine in the endotoxemia and the function of the spleen are discussed.

J Am Vet Med Assoc, 1989 Aug 1, 195(3), 340 - 2
Serratia marcescens septicemia associated with infusion of an amino acid solution in two horses; Young DR et al.; Clinical septicemia developed in 2 clinically normal horses after both were administered a portion of an amino acid solution IV . Serratia marcescens was subsequently isolated from blood of both horses . The isolates were shown to be identical on the basis of antibiograms and plasmid biochemistry, incriminating the infusate as the source of bacterial infection . The horses recovered after supportive and antimicrobial treatment.

J Invertebr Pathol, 1989 Jul, 54(1), 32 - 8
Mortality in adult tsetse, Glossina morsitans morsitans, caused by entomopathogenic bacteria; Kaaya GP et al.; Mortality in adult tsetse, Glossina morsitans morsitans, caused by Pseudomonas aeruginosa, Serratia marcescens, Bacillus sphaericus, Bacillus cereus, Bacillus thuringiensis H-14, B . thuringiensis 1, B . thuringiensis 5, B . thuringiensis var . insraelensis, and Providentia rettgeri was determined . When bacteria were smeared on rabbit skin and tsetse allowed to feed only once on the contaminated area, mortality 8 days postingestion was significantly higher (P less than 0.01) in tsetse fed on P . aeruginosa, S . marcescens, B . thuringiensis 1, and P . rettgeri and increased when tsetse were allowed to feed for the second time on the contaminated skin . With this smear technique, however, mortalities were generally not remarkable . In artificial membrane feeding experiments using low concentrations of bacteria (-10(6)/ml of blood), the B . thuringiensis strains caused low mortality, except B . thuringiensis H-14, which caused 59% mortality . However, at this concentration, P . aeruginosa, S . marcescens, B . cereus, and P . rettgeri caused highly significant (P less than 0.01) mortality (64-96%) . When higher concentrations of bacteria (10(7)/ml) were used, all the bacteria tested, except B . sphaericus, caused high mortality ranging from 70 to 98% . Thus, mortality depended on the species of bacteria, the dose ingested, and time postingestion.

J Clin Lab Immunol, 1989 Jul, 29(3), 125 - 32
Effects of vaccination against systemic Serratia infection; Kumagai Y et al.; Host defense against Serratia marcescens in experimental infection in mice was enhanced by vaccination with formalin-killed bacteria of the same strain . The enhancement appeared within 24 hr after vaccination, reached a peak seven days later and lasted four weeks . The enhanced resistance to Serratia infection was also observed in the early phase (within seven days) after vaccination with killed Escherichia coli or other Gram-negative strains, but the efficacy on Day 7 was inferior to that with killed S . marcescens . Phagocytic activities of both circulating neutrophils and peritoneal macrophages were measured by the chemiluminescence (CL) response, and the activity of tissue macrophages was evaluated by the carbon clearance test . The activities were significantly elevated in the early phase, that is, within two or three days for neutrophils, seven days for peritoneal macrophages and at least 14 days for tissue macrophages, after vaccination with killed Gram-negative bacteria . These results suggest that the enhancement of host defense in the early phase is dependent on phagocytic functions that are non-specifically activated by dead bacteria . In the late phase after vaccination, specific immunity might have been involved in the defense mechanism . However, transfer of high titer specific antiserum, in itself, did not render mice resistant to Serratia infection.

J Endod, 1989 Jul, 15(7), 290 - 3
Bacteriological comparison of ultrasonic and hand instrumentation of root canals in dogs; DeNunzio MS et al.; This study compared the effectiveness of hand and ultrasonic instrumentation for removing a standardized inoculum of pigmented Serratia marcescens from the root canal system of premolars in dogs . Forty-four premolars from nine beagle dogs were divided into two experimental groups of 20 and 24 teeth, respectively . The experimental teeth were inoculated wi