Genetic basis for activity differences between vancomycin and glycolipid derivatives of vancomycin.
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.
Eggert
U S
US
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Ruiz
N
N
Falcone
B V
BV
Branstrom
A A
AA
Goldman
R C
RC
Silhavy
T J
TJ
Kahne
D
D
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
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