Poole K, Srikumar R
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Curr Top Med Chem. 2001 May;1(1):59-71. doi: 10.2174/1568026013395605.
Pseudomonas aeruginosa is an opportunistic human pathogen characterized by an intrinsic resistance to multiple antimicrobial agents and the ability to develop high-level (acquired) multidrug resistance during antibiotic therapy. Much of this resistance is promoted by highly homologous three-component efflux systems of broad substrate specificity, of which four have been identified to date. These include MexA-Mexs-OprM and MexX-MexY-OprM, which are expressed constitutively in wild type cells and, thus, provide for intrinsic multidrug resistance, and MexC-MexD-OprJ and MexE-MexF-OprN, whose expression so far has only been seen in acquired multidrug resistant mutant strains. Additional homologues of these efflux systems are identifiable in the recently released genome sequence, though their roles, if any, in antimicrobial efflux are unknown. These tripartite pumps are composed of an integral cytoplasmic membrane drug-proton antiporter of the resistance-nodulation-cell division (RND) family of exporters, a channel-forming outer membrane efflux protein (or outer membrane factor [OMF]) and a periplasmic membrane fusion protein (MFP) that links the other two. In addition to a number of antimicrobials of clinical significance, these pumps also export dyes, detergents, disinfectants, organic solvents and acylated homoserine lactones involved in quorum-sensing. While the natural functional of these pumps remains undefined, the fact that they contribute to antimicrobial resistance in P. aeruginosa makes them reasonable targets for therapeutic intervention.
铜绿假单胞菌是一种机会性人类病原体，其特征是对多种抗菌药物具有内在抗性，并在抗生素治疗期间能够产生高水平（获得性）多药耐药性。这种耐药性很大程度上是由具有广泛底物特异性的高度同源的三组分外排系统促进的，迄今为止已鉴定出其中四种。这些包括MexA-Mexs-OprM和MexX-MexY-OprM，它们在野生型细胞中组成性表达，因此提供内在的多药耐药性，以及MexC-MexD-OprJ和MexE-MexF-OprN，其表达迄今为止仅在获得性多药耐药突变菌株中出现。在最近发布的基因组序列中可以识别出这些外排系统的其他同源物，尽管它们在抗菌外排中的作用（如果有的话）尚不清楚。这些三方泵由抗性-结瘤-细胞分裂（RND）家族的输出蛋白中的一种整合细胞质膜药物-质子反向转运蛋白、一种形成通道的外膜外排蛋白（或外膜因子[OMF]）和一种连接其他两者的周质膜融合蛋白（MFP）组成。除了许多具有临床意义的抗菌药物外，这些泵还输出参与群体感应的染料、洗涤剂、消毒剂、有机溶剂和酰化高丝氨酸内酯。虽然这些泵的天然功能仍未确定，但它们在铜绿假单胞菌中对抗菌耐药性有贡献这一事实使其成为治疗干预的合理靶点。
