Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants.

Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants.
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DOI:
10.3390/microorganisms4010014
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发表时间:
2016-02-16
期刊:
影响因子:
4.5
通讯作者:
Martinez JL
Martinez JL
中科院分区:
生物学3区
文献类型:
--
作者:
Blanco P;Hernando-Amado S;Reales-Calderon JA;Corona F;Lira F;Alcalde-Rico M;Bernardini A;Sanchez MB;Martinez JL

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细菌多药外排泵是存在于所有微生物中的抗生素耐药性决定因素。除了少数例外,它们是染色体编码的,在遗传和蛋白质水平上都呈现保守的组织。此外,大多数(如果不是全部的话)给定细菌物种的菌株呈现相同的染色体编码的外排泵。总而言之,这表明多药外排泵是细菌基因组中编码的古老元件,早在最近将抗生素用于人类和动物治疗之前。在这方面,值得一提的是,外排泵可以挤出各种各样的底物,除了抗生素之外,还包括重金属、有机污染物、植物产生的化合物、群体感应信号或细菌代谢物等。在目前的审查中,我们目前的信息,多药外排泵可能有不同的功能,在不同的栖息地,以及对它们的特定信号的调节细菌的行为。由于,除了在非临床生态系统中的功能,多药外排泵有助于细菌病原体的内在,获得性和表型耐药性,该审查还提供了关于寻找多药外排泵抑制剂的信息,这些抑制剂目前正在开发中,目的是增加细菌病原体对抗生素的敏感性。
Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy. In this regard, it is worth mentioning that efflux pumps can extrude a wide range of substrates that include, besides antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals or bacterial metabolites, among others. In the current review, we present information on the different functions that multidrug efflux pumps may have for the bacterial behaviour in different habitats as well as on their regulation by specific signals. Since, in addition to their function in non-clinical ecosystems, multidrug efflux pumps contribute to intrinsic, acquired, and phenotypic resistance of bacterial pathogens, the review also presents information on the search for inhibitors of multidrug efflux pumps, which are currently under development, in the aim of increasing the susceptibility of bacterial pathogens to antibiotics.
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