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Antimicrobial Evaluation of Nocathiacins, a Thiazole Peptide Class of Antibiotics. Michael J. Pucci, 2004.Nocathiacins are cyclic thiazolyl peptides with inhibitory activity against gram-positive bacteria . BMS-249524 (nocathiacin I), identified from screening a library of compounds against a multiply antibiotic-resistant Enterococcus faecium strain, was used as a lead chemotype to obtain additional structurally related compounds . The MIC assay results of BMS-249524 and two more water-soluble derivatives, BMS-411886 and BMS-461996, revealed potent in vitro activities against a variety of gram-positive pathogens including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin intermediate-resistant S . aureus, vancomycin-resistant enterococci, Mycobacterium tuberculosis and Mycobacterium avium . Analysis of killing kinetics revealed that these compounds are bactericidal for S . aureus with at least a 3-log10 reduction of bacterial growth within 6 h of exposure to four times the MICs . Nocathiacin-resistant mutants were characterized by DNA sequence analyses . The mutations mapped to the rplK gene encoding the L11 ribosomal protein in the 50S subunit in a region previously shown to be involved in the binding of related thiazolyl peptide antibiotics . These compounds demonstrated potential for further development as a new class of antibacterial agents with activity against key antibiotic-resistant gram-positive bacterial pathogens . High Prevalence of Extended-Spectrum ß-Lactamase-Producing Strains among Blood Isolates of Enterobacter spp . Collected in a Tertiary Hospital during an 8-Year Period and Their Antimicrobial Susceptibility Patterns. Hyunjoo Pai, 2004.Of 72 blood isolates of Enterobacter spp . collected over an 8-year period, 50% (36 of 72) were derepressed or partially derepressed AmpC mutants . The extended-spectrum ß-lactamase (ESBL) production rate was 43% (31 of 72 isolates), and 67.3% (31 of 46) of extended-spectrum cephalosporin-resistant strains produced ESBLs . Thus, a confirmatory test for ESBL production is necessary for extended-spectrum cephalosporin-resistant Enterobacter spp . Cluster of Type IV Secretion Genes in Helicobacter pylori's Plasticity Zone. Dangeruta Kersulyte, 2003.Some genes present in only certain strains of the genetically diverse gastric pathogen Helicobacter pylori may affect its phenotype and/or evolutionary potential . Here we describe a new 16.3-kb segment, 7 of whose 16 open reading frames are homologs of type IV secretion genes (virB4, virB7 to virB11, and virD4), the third such putative secretion gene cluster found in H . pylori . This segment, to be called tfs3, was discovered by subtractive hybridization and chromosome walking . Full-length and truncated tfs3 elements were found in 20 and 19%, respectively, of 94 strains tested, which were from Spain, Peru, India, and Japan . A tfs3 remnant (6 kb) was found in an archived stock of reference strain J99, although it was not included in this strain's published genome sequence . PCR and DNA sequence analyses indicated the following . (i) tfs3's ends are conserved . (ii) Right-end insertion occurred at one specific site in a chromosomal region that is varied in gene content and arrangement, the "plasticity zone." (iii) Left-end insertion occurred at different sites in each of nine strains studied . (iv) Sequences next to the right-end target in tfs3-free strains were absent from most strains carrying full-length tfs3 elements . These patterns suggested insertion by a transposition-like event, but one in which targets are chosen with little or no specificity at the left end and high specificity at the right end, thereby deleting the intervening DNA . A Francisella tularensis Pathogenicity Island Required for Intramacrophage Growth. Francis E. Nano, 2004.Francisella tularensis is a gram-negative, facultative intracellular pathogen that causes the highly infectious zoonotic disease tularemia . We have discovered a ca . 30-kb pathogenicity island of F . tularensis (FPI) that includes four large open reading frames (ORFs) of 2.5 to 3.9 kb and 13 ORFs of 1.5 kb or smaller . Previously, two small genes located near the center of the FPI were shown to be needed for intramacrophage growth . In this work we show that two of the large ORFs, located toward the ends of the FPI, are needed for virulence . Although most genes in the FPI encode proteins with amino acid sequences that are highly conserved between high- and low-virulence strains, one of the FPI genes is present in highly virulent type A F . tularensis, absent in moderately virulent type B F . tularensis, and altered in F . tularensis subsp . novicida, which is highly virulent for mice but avirulent for humans . The G+C content of a 17.7-kb stretch of the FPI is 26.6%, which is 6.6% below the average G+C content of the F . tularensis genome . This extremely low G+C content suggests that the DNA was imported from a microbe with a very low G+C-containing chromosome . Novel Eukaryotes from the Permanently Anoxic Cariaco Basin (Caribbean Sea). Thorsten Stoeck, 2003.Present knowledge of microbial diversity is decidedly incomplete (S . J . Giovannoni and M . S . Rappé, p . 47-84, in D . Kirchman, ed., Microbial Ecology of the Oceans, 2000; E . Stackebrandt and T . M . Embley, p . 57-75, in R . R . Colwell and D . J . Grimes, ed., Nonculturable Microorganisms in the Environment, 2000) . Protistan phylogenies are particularly deficient and undoubtedly exclude clades of principal ecological and evolutionary importance (S . L . Baldauf, Science 300:1703-1706, 2003) . The rRNA approach has been extraordinarily successful in expanding the global prokaryotic record (S . J . Giovannoni and M . S . Rappé, p . 47-84, in D . Kirchman, ed., Microbial Ecology of the Oceans, 2000; E . Stackebrandt and T . M . Embley, p . 57-75, in R . R . Colwell and D . J . Grimes, ed., Nonculturable Microorganisms in the Environment, 2000) but has rarely been used in protistan discovery . Here we report the first application of the 18S rRNA approach to a permanently anoxic environment, the Cariaco Basin off the Venezuelan coast . On the basis of rRNA sequences, we uncovered a substantial number of novel protistan lineages . These included new clades of the highest taxonomic level unrelated to any known eukaryote as well as deep branches within established protistan groups . Three novel lineages branch at the base of the eukaryotic evolutionary tree preceding, contemporary with, or immediately following the earliest eukaryotic branches . These newly discovered protists may retain traits reminiscent of an early eukaryotic ancestor(s) .
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