Department of Biochemistry, University of Cambridge, Cambridge, UK.
Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
Nat Rev Microbiol. 2018 Sep;16(9):523-539. doi: 10.1038/s41579-018-0048-6.
Infections arising from multidrug-resistant pathogenic bacteria are spreading rapidly throughout the world and threaten to become untreatable. The origins of resistance are numerous and complex, but one underlying factor is the capacity of bacteria to rapidly export drugs through the intrinsic activity of efflux pumps. In this Review, we describe recent advances that have increased our understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria. Clinical and laboratory data indicate that efflux pumps function not only in the drug extrusion process but also in virulence and the adaptive responses that contribute to antimicrobial resistance during infection. The emerging picture of the structure, function and regulation of efflux pumps suggests opportunities for countering their activities.
由多药耐药性病原菌引起的感染正在全球范围内迅速传播,并有可能变得无法治疗。耐药性的产生原因众多且复杂,但一个潜在因素是细菌通过内在的外排泵活性快速将药物排出。在这篇综述中,我们描述了最近的进展,这些进展增加了我们对细菌中多药外排泵的结构和分子机制的理解。临床和实验室数据表明,外排泵不仅在药物排出过程中起作用,而且在毒力和适应性反应中起作用,这些反应有助于感染期间对抗微生物药物的耐药性。对外排泵的结构、功能和调节的新认识为对抗其活性提供了机会。