Efflux as a mechanism of resistance to antimicrobials in Pseudomonas aeruginosa and related bacteria: unanswered questions.

Efflux as a mechanism of resistance to antimicrobials in Pseudomonas aeruginosa and related bacteria: unanswered questions.
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发表时间:
2003-03
期刊:
Genetics and molecular research : GMR
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通讯作者:
H. Schweizer
H. Schweizer
中科院分区:
其他
文献类型:
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作者:
H. Schweizer

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铜绿假单胞菌是一种机会致病菌,对多种抗菌药表现出先天耐药。这种内在的多药耐药是由低通透性的外膜和许多广泛特异的多药外排系统(MEX)的表达协同引起的,包括MexAB-OprM和Mexxy-OprM。除了这种固有的耐药性,这些系统和另外三个系统,MexCD-OprJ,MexEF-OprN和MexJK-OprM,由于突变事件导致外排基因的过度表达,促进了获得性多药耐药。除抗生素外,这些泵还出口杀菌剂、染料、洗涤剂、代谢抑制剂、有机溶剂和参与细菌细胞间通讯的分子。在洋葱伯克霍尔德氏菌、假鼻疽杆菌、嗜麦芽窄食单胞菌和非病原菌恶臭假单胞菌中已发现铜绿假单胞菌耐药-结瘤-分裂系统的同系物,它们在抗菌剂和/或有机溶剂的抗药性中发挥作用。尽管在过去的几年里对这些多药外排系统进行了深入的研究,但它们的确切分子结构、表达调控方式和自然功能在很大程度上仍不清楚。
Pseudomonas aeruginosa is an opportunistic human pathogen exhibiting innate resistance to multiple antimicrobial agents. This intrinsic multidrug resistance is caused by synergy between a low-permeability outer membrane and expression of a number of broadly-specific multidrug efflux (Mex) systems, including MexAB-OprM and MexXY-OprM. In addition to this intrinsic resistance, these and three additional systems, MexCD-OprJ, MexEF-OprN and MexJK-OprM promote acquired multidrug resistance as a consequence of hyper-expression of the efflux genes by mutational events. In addition to antibiotics, these pumps export biocides, dyes, detergents, metabolic inhibitors, organic solvents and molecules involved in bacterial cell-cell communication. Homologues of the resistance-nodulation-division systems of P. aeruginosa have been found in Burkholderia cepacia, B. pseudomallei, Stenotrophomonas maltophilia, and the nonpathogen P. putida, where they play roles in resistance to antimicrobials and/or organic solvents. Despite intensive studies of these multidrug efflux systems over the past several years, their precise molecular architectures, their modes of regulation of expression and their natural functions remain largely unknown.