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Journal of Bacteriology, September 2008, p. 5981-5988, Vol. 190, No. 17
0021-9193/08/$08.00+0     doi:10.1128/JB.01982-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Determination of Antibiotic Hypersensitivity among 4,000 Single-Gene-Knockout Mutants of Escherichia coli{triangledown} ,{dagger}

Cindy Tamae, Anne Liu, Katherine Kim, Daniel Sitz, Jeeyoon Hong, Elinne Becket, Ann Bui, Parrisa Solaimani, Katherine P. Tran, Hanjing Yang, and Jeffrey H. Miller*

Department of Microbiology, Immunology, and Molecular Genetics, the Molecular Biology Institute, and the David Geffen School of Medicine, University of California, Los Angeles, California 90095

Received 20 December 2007/ Accepted 30 June 2008

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.

* Corresponding author. Mailing address: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095. Phone: (310) 825-8460. Fax: (310) 206-3088. E-mail: jhmiller{at}microbio.ucla.edu

{triangledown} Published ahead of print on 11 July 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, September 2008, p. 5981-5988, Vol. 190, No. 17
0021-9193/08/$08.00+0     doi:10.1128/JB.01982-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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