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Determination of Antibiotic Hypersensitivity among 4,000 Single-Gene-Knockout Mutants of Escherichia coli
Open accessAbstract
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.
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Cites
Construction of Escherichia coli K‐12 in‐frame, single‐gene knockout mutants: the Keio collection
Baba, T., Ara, T., Hasegawa, M., Takai, Y., Okumura, Y., Baba, M., Datsenko, K. A., Tomita, M., Wanner, B. L., & Mori, H. (2006) · Molecular Systems Biology · doi:10.1038/msb4100050 · Cited by 7,858
Determination of minimum inhibitory concentrations
Andrews, J. M. (2001) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/48.suppl_1.5 · Cited by 4,129
Multicomponent therapeutics for networked systems
Keith, C. T., Borisy, A. A., & Stockwell, B. R. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1609 · Cited by 769
Cited by
Origins and evolution of antibiotic resistance
Davies, J., & Davies, D. (2010) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00016-10 · Cited by 5,784
Call of the wild: antibiotic resistance genes in natural environments
Allen, H. K., Donato, J., Wang, H. H., Cloud-Hansen, K. A., Davies, J., & Handelsman, J. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2312 · Cited by 2,361
Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions
Cox, G., & Wright, G. D. (2013) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2013.02.009 · Cited by 697
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Ivask, A., ElBadawy, A., Kaweeteerawat, C., Boren, D., Fischer, H., Ji, Z., Chang, C. H., Liu, R., Tolaymat, T., Telesca, D., et al. (2014) · ACS Nano · doi:10.1021/nn4044047 · Cited by 599
Imamovic, L., & Sommer, M. O. A. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006609 · Cited by 444
Metadata
- Authors
- Tamae, C., Liu, A., Kim, K., Sitz, D., Hong, J., Becket, E., Bui, A., Solaimani, P., Tran, K. P., Yang, H., & Miller, J. H.
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2008-09
- Volume
- 190
- Issue
- 17
- Pages
- 5981-5988
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- OpenAlex
- W2115049154
- Cited by
- 234
- References
- 3
- FWCI
- 7.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Tamae, C., Liu, A., Kim, K., Sitz, D., Hong, J., Becket, E., Bui, A., Solaimani, P., Tran, K. P., Yang, H., & Miller, J. H. (2008). Determination of Antibiotic Hypersensitivity among 4,000 Single-Gene-Knockout Mutants of Escherichia coli. Journal of Bacteriology. https://doi.org/10.1128/jb.01982-07
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