Rieg Siegbert, Huth Anja, Kalbacher Hubert, Kern Winfried V
Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital, Freiburg, Germany.
Int J Antimicrob Agents. 2009 Feb;33(2):174-6. doi: 10.1016/j.ijantimicag.2008.07.032. Epub 2008 Oct 21.
The role of clinically important multidrug resistance (MDR) efflux pumps in bacterial resistance to various human antimicrobial peptides (AMPs), including cathelicidin LL-37, the alpha-defensins human neutrophil peptides (HNPs)-1-3 and HD-5 and the beta-defensins hBD-2 and -3, was investigated. AMP susceptibility testing was performed by killing assays and standard minimal inhibitory concentration assays. AMP susceptibility was determined in Escherichia coli and Pseudomonas aeruginosa strains overexpressing resistance-nodulation-cell division (RND)-type pumps AcrAB and MexAB, respectively, and in their pump-deficient parental strains. Furthermore, the impact of a member of the major facilitator (MF) efflux pump family was investigated in Staphylococcus aureus overexpressing NorA and in wild-type strains. The E. coli AcrAB and P. aeruginosa MexAB RND-type efflux pumps as well as the S. aureus NorA MF efflux pump were unable to confer resistance to AMPs. These findings do not support a critical role of MDR efflux pumps in the tested pathogens as a strategy to increase virulence by circumventing the antimicrobial action of innate defence AMPs.
研究了临床上重要的多药耐药（MDR）外排泵在细菌对多种人类抗菌肽（AMP）的耐药性中的作用，这些抗菌肽包括cathelicidin LL-37、α-防御素人类中性粒细胞肽（HNP）-1-3和HD-5以及β-防御素hBD-2和hBD-3。通过杀菌试验和标准最小抑菌浓度试验进行AMP敏感性测试。分别在过表达耐药-结瘤-细胞分裂（RND）型泵AcrAB和MexAB的大肠杆菌和铜绿假单胞菌菌株及其泵缺陷亲本菌株中测定AMP敏感性。此外，还研究了主要易化子（MF）外排泵家族的一个成员在过表达NorA的金黄色葡萄球菌和野生型菌株中的影响。大肠杆菌AcrAB和铜绿假单胞菌MexAB RND型外排泵以及金黄色葡萄球菌NorA MF外排泵均不能赋予对AMP的耐药性。这些发现不支持MDR外排泵在受试病原体中作为一种通过规避天然防御AMP的抗菌作用来增加毒力的策略的关键作用。
