Blair Jessica M A, Piddock Laura J V
Antimicrobial Agents Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Curr Opin Microbiol. 2009 Oct;12(5):512-9. doi: 10.1016/j.mib.2009.07.003. Epub 2009 Aug 5.
Resistance nodulation division efflux systems have a major role in both intrinsic and acquired multi-drug resistance in Gram-negative bacteria. The recent structure of an assembled tripartite system, AcrAB-TolC, revealed that AcrB is docked onto TolC, which remains in an open state once part of the assembled complex and three AcrA molecules complete the structure. This is in contrast to data for the MexAB-OprM system of P. aeruginosa that, depending on pH, has between two and six MexA molecules per OprM trimer. RND systems are also important for pathogenicity of several bacteria and for Salmonellae lacking components of AcrAB-TolC, expression of known virulence determinants were significantly altered. The importance of these systems in both MDR and pathogenicity has made RND systems the target of new drugs aimed at inhibiting their function. The wealth of new structural and functional data will inform rational drug design.
耐药-结瘤-分裂外排系统在革兰氏阴性菌的固有和获得性多药耐药中起主要作用。最近组装好的三方系统AcrAB-TolC的结构表明，AcrB对接在TolC上，一旦成为组装复合物的一部分，TolC就会保持开放状态，并且三个AcrA分子会完成该结构。这与铜绿假单胞菌的MexAB-OprM系统的数据形成对比，该系统根据pH值，每个OprM三聚体有2至6个MexA分子。RND系统对几种细菌的致病性也很重要，对于缺乏AcrAB-TolC组件的沙门氏菌，已知毒力决定因素的表达会发生显著改变。这些系统在多药耐药和致病性方面的重要性使RND系统成为旨在抑制其功能的新药的靶点。丰富的新结构和功能数据将为合理的药物设计提供依据。
