PMID:18621901

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Citation

Tamae, C, Liu, A, Kim, K, Sitz, D, Hong, J, Becket, E, Bui, A, Solaimani, P, Tran, KP, Yang, H and Miller, JH (2008) Determination of antibiotic hypersensitivity among 4,000 single-gene-knockout mutants of Escherichia coli.J. Bacteriol. 190:5981-8

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.

Links

PubMed Online version:10.1128/JB.01982-07

Keywords

Ampicillin; Anti-Bacterial Agents; Ciprofloxacin; Escherichia coli; Genes, Bacterial; Gentamicins; Metronidazole; Microbial Sensitivity Tests; Mutation; Rifampin; Sulfamethoxazole; Vancomycin

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Materials and Methods Used

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Phenotype of Taxon Information Genotype Information (if known) Condition Information OMP ID OMP Term Name ECO ID ECO Term Name Notes Status

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