Escherichia coli genes that reduce the lethal effects of stress

BMC Microbiology

Research Article

Xilin Zhao¹  Muhammad Malik¹  Karl Drlica¹  Jian-Ying Wang¹  Angella Dorsey-Oresto¹  Xiulin Han²  Tao Lu³ 

[1] Public Health Research Institute, New Jersey Medical School, UMDNJ, 225 Warren Street, NJ 07103, Newark, USA;Yunnan Institute of Microbiology, Yunnan University, 52 Cui Hu Bei Lu, 650091, Kunming, Yunnan, PR China;Yunnan Institute of Microbiology, Yunnan University, 52 Cui Hu Bei Lu, 650091, Kunming, Yunnan, PR China;Public Health Research Institute, New Jersey Medical School, UMDNJ, 225 Warren Street, NJ 07103, Newark, USA;

关键词: Sodium Dodecyl Sulfate;    Norfloxacin;    Nalidixic Acid;    Lethal Effect;    Yersinia Enterocolitica;   

DOI  :  10.1186/1471-2180-10-35

 received in 2009-07-03, accepted in 2010-02-04,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe continuing emergence of antimicrobial resistance requires the development of new compounds and/or enhancers of existing compounds. Genes that protect against the lethal effects of antibiotic stress are potential targets of enhancers. To distinguish such genes from those involved in drug uptake and efflux, a new susceptibility screen is required.ResultsTransposon (Tn5)-mediated mutagenesis was used to create a library of Escherichia coli mutants that was screened for hypersensitivity to the lethal action of quinolones and counter-screened to have wild-type bacteriostatic susceptibility. Mutants with this novel "hyperlethal" phenotype were found. The phenotype was transferable to other E. coli strains by P1-mediated transduction, and for a subset of the mutants the phenotype was complemented by the corresponding wild-type gene cloned into a plasmid. Thus, the inactivation of these genes was responsible for hyperlethality. Nucleotide sequence analysis identified 14 genes, mostly of unknown function, as potential factors protecting from lethal effects of stress. The 14 mutants were killed more readily than wild-type cells by mitomycin C and hydrogen peroxide; nine were also more readily killed by UV irradiation, and several exhibited increased susceptibility to killing by sodium dodecyl sulfate. No mutant was more readily killed by high temperature.ConclusionsA new screening strategy identified a diverse set of E. coli genes involved in the response to lethal antimicrobial and environmental stress, with some genes being involved in the response to multiple stressors. The gene set, which differed from sets previously identified with bacteriostatic assays, provides an entry point for obtaining small-molecule enhancers that will affect multiple antimicrobial agents.

【 授权许可】

Unknown   
© Han et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.