Nishino Kunihiko, Senda Yasuko, Yamaguchi Akihito
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan.
J Antibiot (Tokyo). 2008 Mar;61(3):120-7. doi: 10.1038/ja.2008.120.
Multidrug efflux pumps contribute to the resistance of Escherichia coli against many antibiotics and biocides. Here, we report that the CRP regulator modulates multidrug resistance in E. coli through repression of the genes encoding the MdtEF multidrug efflux pump. Screening of mutants for ability to increase beta-lactam resistance in E. coli led to the identification of a mutation in crp, which codes for the major global regulator of catabolite-sensitive operons. Deletion of crp significantly increased the resistance of the E. coli strain to oxacillin, azithromycin, erythromycin and crystal violet. The increase in drug resistance caused by crp deletion was completely suppressed by deletion of the multifunctional outer membrane channel gene tolC. TolC interacts with different drug efflux pumps. Among the twenty drug efflux pumps in E. coli, quantitative real-time PCR analysis showed that CRP repressed the expression of mdtEF. Deletion of mdtEF completely suppressed CRP-modulated multidrug resistance. Therefore, in addition to its role in catabolite control, CRP contributes to multidrug resistance in E. coli. Our results indicate that the CRP regulator modulates multidrug resistance in E. coli by repressing expression of the MdtEF multidrug efflux pump.
多药外排泵导致大肠杆菌对多种抗生素和杀菌剂产生耐药性。在此，我们报告CRP调节因子通过抑制编码MdtEF多药外排泵的基因来调节大肠杆菌中的多药耐药性。筛选能增加大肠杆菌β-内酰胺耐药性的突变体，导致鉴定出crp中的一个突变，crp编码分解代谢敏感操纵子的主要全局调节因子。缺失crp显著增加了大肠杆菌菌株对奥沙西林、阿奇霉素、红霉素和结晶紫的耐药性。crp缺失导致的耐药性增加被多功能外膜通道基因tolC的缺失完全抑制。TolC与不同的药物外排泵相互作用。在大肠杆菌的20种药物外排泵中，定量实时PCR分析表明CRP抑制mdtEF的表达。缺失mdtEF完全抑制了CRP调节的多药耐药性。因此，除了其在分解代谢控制中的作用外，CRP还导致大肠杆菌的多药耐药性。我们的结果表明，CRP调节因子通过抑制MdtEF多药外排泵的表达来调节大肠杆菌中的多药耐药性。
