PMID:11520949

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Citation

Eggert, US, Ruiz, N, Falcone, BV, Branstrom, AA, Goldman, RC, Silhavy, TJ and Kahne, D (2001) Genetic basis for activity differences between vancomycin and glycolipid derivatives of vancomycin. Science 294:361-4

Abstract

Small molecules that affect specific protein functions can be valuable tools for dissecting complex cellular processes. Peptidoglycan synthesis and degradation is a process in bacteria that involves multiple enzymes under strict temporal and spatial regulation. We used a set of small molecules that inhibit the transglycosylation step of peptidoglycan synthesis to discover genes that help to regulate this process. We identified a gene responsible for the susceptibility of Escherichia coli cells to killing by glycolipid derivatives of vancomycin, thus establishing a genetic basis for activity differences between these compounds and vancomycin.

Links

PubMed Online version:10.1126/science.1063611

Keywords

Anti-Bacterial Agents/chemistry; Anti-Bacterial Agents/pharmacology; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Drug Resistance, Microbial; Drug Resistance, Multiple; Enzyme Inhibitors/pharmacology; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/growth & development; Genes, Bacterial; Genetic Complementation Test; Glycosylation; Hexosyltransferases/antagonists & inhibitors; Lipoproteins/genetics; Lipoproteins/metabolism; Microbial Sensitivity Tests; Mutation; N-Acetylmuramoyl-L-alanine Amidase/metabolism; Oligosaccharides/chemistry; Oligosaccharides/pharmacology; Peptidoglycan/biosynthesis; Peptidoglycan Glycosyltransferase; Phenotype; Vancomycin/analogs & derivatives; Vancomycin/chemistry; Vancomycin/pharmacology; Vancomycin Resistance/genetics

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