主动外排:杀菌剂和抗生素耐药性的常见机制。

S B Levy
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引用次数: 0

摘要

能量驱动的药物外排系统越来越被认为是抗生素耐药的机制。染色体位于细菌或由细菌获得,它们可以被环境信号或调节基因的突变激活。主要有两大类:以质子动力为动力的系统和依赖ATP的系统。这些泵可能具有有限的或广泛的底物,即所谓的多重耐药泵,它们本身形成了许多相关的家族。大肠杆菌和肠杆菌科其他成员的多重抗生素耐药位点和mar调控子是导致外排泵表达增加的广义反应位点的范例。AcrAB泵就是这样一种泵,它可以挤出三氯生、氯己定、季铵化合物等杀菌剂以及多种抗生素。在铜绿假单胞菌中,许多多药外排泵输出广泛的底物。由于表达这些泵的细菌阻碍了控制传染病的两种治疗剂————防止传染病剂传播的杀菌剂和治疗和治愈传染病的抗生素————的效力,因此它们特别值得关注。谨慎使用抗生素和杀菌剂将防止耐药突变体的选择和繁殖,并保持这些有价值的抗感染药物的功效。
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Active efflux, a common mechanism for biocide and antibiotic resistance.

Energy-driven drug efflux systems are increasingly recognized as mechanisms of antibiotic resistance. Chromosomally located or acquired by bacteria, they can either be activated by environmental signals or by a mutation in a regulatory gene. Two major categories exist: those systems energized by proton motive force and those dependent on ATP. The pumps may have limited or broad substrates, the so-called multiple drug resistance pumps, which themselves form a number of related families. The multiple antibiotic resistance (mar) locus and mar regulon in Escherichia coli and other members of the Enterobacteriaceae is a paradigm for a generalized response locus leading to increased expression of efflux pumps. One such pump, the AcrAB pump extrudes biocides such as triclosan, chlorhexidine and quaternary ammonium compounds as well as multiple antibiotics. In Pseudomonas aeruginosa, a number of multidrug efflux pumps export a broad range of substrates. Since bacteria expressing these pumps thwart the efficacy of both kinds of therapeutic agents which control infectious diseases--biocides which prevent transmission of infectious disease agents and antibiotics which treat and cure infectious diseases--they are of particular concern. The prudent use of antibiotics and biocides will guard against the selection and propagation of drug-resistant mutants and preserve the efficacy of these valuable anti-infective agents.

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