title: Genetic basis for activity differences between vancomycin and glycolipid derivatives of vancomycin.
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.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
authors.forename: U S
authors.initials: US
authors.lastname: Eggert
authors.forename: N
authors.initials: N
authors.lastname: Ruiz
authors.forename: B V
authors.initials: BV
authors.lastname: Falcone
authors.forename: A A
authors.initials: AA
authors.lastname: Branstrom
authors.forename: R C
authors.initials: RC
authors.lastname: Goldman
authors.forename: T J
authors.initials: TJ
authors.lastname: Silhavy
authors.forename: D
authors.initials: D
authors.lastname: Kahne
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006031:Glycosylation; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology; D010457:Peptidoglycan / Q000096:biosynthesis*; D046928:Peptidoglycan Glycosyltransferase; D010641:Phenotype; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008074:Lipoproteins; D009844:Oligosaccharides; D010457:Peptidoglycan; C437984:chlorobiphenyl vancomycin; C405766:chlorobiphenyl-desleucyl-vancomycin; D014640:Vancomycin; D006602:Hexosyltransferases; D046928:Peptidoglycan Glycosyltransferase; D009238:N-Acetylmuramoyl-L-alanine Amidase; C419802:moenomycin