Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and related organisms.
Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and related organisms.
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发表时间：
2001-04
影响因子：
1.2
通讯作者：
K. Poole
中科院分区：
文献类型：
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作者：
K. Poole
铜绿假单胞菌是一种机会性的人类病原体，具有对多种抗菌药的先天耐药性。许多广谱的多药外排系统，包括MexAB-OprM和Mexxy-OprM，是造成这种内在多药耐药的主要原因。此外，这些和另外两个三方外排系统，MexCD-OprJ和MexEF-OprN，由于外排基因的突变过表达，促进了获得性多药耐药。除了抗生素，这些泵还促进了与群体感应有关的许多染料、洗涤剂、抑制剂、消毒剂、有机溶剂和高丝氨酸内酯的出口。外排泵蛋白具有很高的同源性，由抗性结瘤分裂(RND)家族的细胞膜相关药物质子逆向转运蛋白、外膜通道形成蛋白[有时称为外膜因子(OMF)]和周膜融合蛋白(MFP)组成。这些系统的同系物已经在嗜麦芽窄食单胞菌、洋葱伯克霍尔德氏菌、假腮腺伯克霍尔德氏菌和非病原体恶臭假单胞菌中被描述，它们在多种抗菌剂和/或有机溶剂的出口和耐药性中发挥作用。尽管这些多药外排系统的自然功能在很大程度上尚不清楚，但它们对抗生素耐药性的贡献以及它们在一些重要的人类病原体中的保守使它们成为治疗干预的合理靶点。
Pseudomonas aeruginosa is an opportunistic human pathogen characterized by an innate resistance to multiple antimicrobial agents. A major contribution to this intrinsic multidrug resistance is provided by a number of broadly-specific multidrug efflux systems, including MexAB-OprM and MexXY-OprM. In addition, these and two additional tripartite efflux systems, MexCD-OprJ and MexEF-OprN, promote acquired multidrug resistance as a result of mutational hyperexpression of the efflux genes. In addition to antibiotics, these pumps promote export of numerous dyes, detergents, inhibitors, disinfectants, organic solvents and homoserine lactones involved in quorum sensing. The efflux pump proteins are highly homologous and consist of a cytoplasmic membrane-associated drug-proton antiporter of the Resistance-Nodulation-Division (RND) family, an outer membrane channel-forming protein [sometimes called outer membrane factor (OMF)] and a periplasmic membrane fusion protein (MFP). Homologues of these systems have been described in Stenotrophomonas maltophilia, Burkholderia cepacia, Burkholderia pseudomallei and the non-pathogen Pseudomonas putida, where they play a role in export of and resistance to multiple antimicrobial agents and/or organic solvents. Although the natural function of these multidrug efflux systems is largely unknown, their contribution to antibiotic resistance and their conservation in a number of important human pathogens makes them logical targets for therapeutic intervention.