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In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium spp.. Ellie J. C. Goldstein, 2004.Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures . Plates with daptomycin were supplemented with Ca2+ to 50 mg/liter . The MICs at which 90% of isolates tested were inhibited (MIC90s) for telavancin and vancomycin were as follows: Actinomyces spp . (n = 45), 0.25 and 1 µg/ml, respectively; Clostridium difficile (n = 14), 0.25 and 1 µg/ml, respectively; Clostridium ramosum (n = 16), 1 and 4 µg/ml, respectively; Clostridium innocuum (n = 15), 4 and 16 µg/ml, respectively; Clostridium clostridioforme (n = 15), 8 and 1 µg/ml, respectively; Eubacterium group (n = 33), 0.25 and 2 µg/ml, respectively; Lactobacillus spp . (n = 26), 0.5 and 4 µg/ml, respectively; Propionibacterium spp . (n = 34), 0.125 and 0.5 µg/ml, respectively; Peptostreptococcus spp. (n = 52), 0.125 and 0.5 µg/ml, respectively; and Corynebacterium spp . (n = 31), 0.03 and 0.5 µg/ml, respectively . The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three- to fivefold more active. Daptomycin had decreased activity (MIC > 4 µg/ml) against 14 strains of Actinomyces spp . and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains . Linezolid showed decreased activity (MIC > 4 µg/ml) against C . ramosum, two strains of C . difficile, and 15 strains of Lactobacillus spp . Imipenem and piperacillin-tazobactam were active against >98% of strains . The MICs of ampicillin for eight Clostridium spp . and three strains of L. casei were >1 µg/ml . The MIC90 of TD-6424 for all strains tested was  2 µg/ml . TD-6424
has potential for use against infections with gram-positive anaerobes
and deserves further clinical
evaluation .
Formation of Protoanemonin from 2-Chloro-cis,cis-Muconate by the Combined Action of Muconate Cycloisomerase and Muconolactone Isomerase. Anke Skiba, 2002.Muconate cycloisomerases are known to catalyze the reversible conversion of 2-chloro-cis,cis-muconate by 1,4- and 3,6-cycloisomerization into (4S)-(+)-2-chloro- and (4R/5S)-(+)-5-chloromuconolactone . 2-Chloromuconolactone is transformed by muconolactone isomerase with concomitant dechlorination and decarboxylation into the antibiotic protoanemonin . The low kcat for this compound compared to that for 5-chloromuconolactone suggests that protoanemonin formation is of minor importance . However, since 2-chloromuconolactone is the initially predominant product of 2-chloromuconate cycloisomerization, significant amounts of protoanemonin were formed in reaction mixtures containing large amounts of muconolactone isomerase and small amounts of muconate cycloisomerase . Such enzyme ratios resemble those observed in cell extracts of benzoate-grown cells of Ralstonia eutropha JMP134 . In contrast, cis-dienelactone was the predominant product formed by enzyme preparations, in which muconolactone isomerase was in vitro rate limiting . In reaction mixtures containing chloromuconate cycloisomerase and muconolactone isomerase, only minute amounts of protoanemonin were detected, indicating that only small amounts of 2-chloromuconolactone were formed by cycloisomerization and that chloromuconate cycloisomerase actually preferentially catalyzes a 3,6-cycloisomerization . Complete Sequence of Virulence Plasmid pJM1 from the Marine Fish Pathogen Vibrio anguillarum Strain 775. Manuela Di Lorenzo, 2003.The virulence plasmid pJM1 enables the fish pathogen Vibrio anguillarum, a gram-negative polarly flagellated comma-shaped rod bacterium, to cause a highly fatal hemorrhagic septicemic disease in salmonids and other fishes, leading to epizootics throughout the world . The pJM1 plasmid 65,009-nucleotide sequence, with an overall G+C content of 42.6%, revealed genes and open reading frames (ORFs) encoding iron transporters, nonribosomal peptide enzymes, and other proteins essential for the biosynthesis of the siderophore anguibactin . Of the 59 ORFs, approximately 32% were related to iron metabolic functions . The plasmid pJM1 confers on V . anguillarum the ability to take up ferric iron as a complex with anguibactin from a medium in which iron is chelated by transferrin, ethylenediamine-di(o-hydroxyphenyl-acetic acid), or other iron-chelating compounds . The fatDCBA-angRT operon as well as other downstream biosynthetic genes is bracketed by the homologous ISV-A1 and ISV-A2 insertion sequences . Other clusters on the plasmid also show an insertion element-flanked organization, including ORFs homologous to genes involved in the biosynthesis of 2,3-dihydroxybenzoic acid . Homologues of replication and partition genes are also identified on pJM1 adjacent to this region . ORFs with no known function represent approximately 30% of the pJM1 sequence . The insertion sequence elements in the composite transposon-like structures, corroborated by the G+C content of the pJM1 sequence, suggest a modular composition of plasmid pJM1, biased towards acquisition of modules containing genes related to iron metabolic functions . We also show that there is considerable microheterogeneity in pJM1-like plasmids from virulent strains of V . anguillarum isolated from different geographical sources . Multiplex Real-Time PCR for Monitoring Heterobasidion annosum Colonization in Norway Spruce Clones That Differ in Disease Resistance. Ari M. Hietala, 2003.A multiplex real-time PCR assay was developed to monitor the dynamics of the Picea abies-Heterobasidion annosum pathosystem . Tissue cultures and 32-year-old trees with low or high resistance to this pathogen were used as the host material . Probes and primers were based on a laccase gene for the pathogen and a polyubiquitin gene for the host . The real-time PCR procedure was compared to an ergosterol-based quantification method in a tissue culture experiment, and there was a strong correlation (product moment correlation coefficient, 0.908) between the data sets . The multiplex real-time PCR procedure had higher resolution and sensitivity during the early stages of colonization and also could be used to monitor the host . In the tissue culture experiment, host DNA was degraded more rapidly in the clone with low resistance than in the clone with high resistance . In the field experiment, the lesions elicited were not strictly proportional to the area colonized by the pathogen . Fungal colonization was more restricted and localized in the lesion in the clone with high resistance, whereas in the clone with low resistance, the fungus could be detected until the visible end of the lesion . Thus, the real-time PCR assay gives better resolution than does the traditionally used lesion length measurement when screening host clones for resistance .
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