title: Determination of antibiotic hypersensitivity among 4,000 single-gene-knockout mutants of Escherichia coli.
abstract: We have tested the entire Keio collection of close to 4,000 single-gene knockouts in Escherichia coli for increased susceptibility to one of seven different antibiotics (ciprofloxacin, rifampin, vancomycin, ampicillin, sulfamethoxazole, gentamicin, or metronidazole). We used high-throughput screening of several subinhibitory concentrations of each antibiotic and reduced more than 65,000 data points to a set of 140 strains that display significantly increased sensitivities to at least one of the antibiotics, determining the MIC in each case. These data provide targets for the design of "codrugs" that can potentiate existing antibiotics. We have made a number of double mutants with greatly increased sensitivity to ciprofloxacin, and these overcome the resistance generated by certain gyrA mutations. Many of the gene knockouts in E. coli are hypersensitive to more than one antibiotic. Together, all of these data allow us to outline the cell's "intrinsic resistome," which provides innate resistance to antibiotics.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Tamae
authors.forename: Anne
authors.initials: A
authors.lastname: Liu
authors.forename: Katherine
authors.initials: K
authors.lastname: Kim
authors.forename: Daniel
authors.initials: D
authors.lastname: Sitz
authors.forename: Jeeyoon
authors.initials: J
authors.lastname: Hong
authors.forename: Elinne
authors.initials: E
authors.lastname: Becket
authors.forename: Ann
authors.initials: A
authors.lastname: Bui
authors.forename: Parrisa
authors.initials: P
authors.lastname: Solaimani
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Tran
authors.forename: Hanjing
authors.initials: H
authors.lastname: Yang
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miller
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics*; D005839:Gentamicins / Q000494:pharmacology; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology; D013420:Sulfamethoxazole / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D008795:Metronidazole; D002939:Ciprofloxacin; D014640:Vancomycin; D000667:Ampicillin; D013420:Sulfamethoxazole; D012293:Rifampin