Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73072, USA.
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73072, USA.
Curr Opin Microbiol. 2022 Oct;69:102179. doi: 10.1016/j.mib.2022.102179. Epub 2022 Jul 23.
Bacterial drug-efflux transporters act synergistically with diffusion barriers of cellular membranes and other resistance mechanisms to protect cells from antibiotics and toxic metabolites. Their critical roles in clinical antibiotic and multidrug resistance are well established. In addition, a large body of evidence has been accumulated in support of their important contributions to bacterial growth and proliferation during infections. However, how these diverse functions of drug transporters are integrated at the level of bacterial cell physiology remains unclear. This opinion briefly summarizes the current understanding of substrate specificities and physiological roles of drug-efflux pumps from Resistance-Nodulation-Division (RND) superfamily of proteins in two ESKAPE pathogens Pseudomonas aeruginosa and Acinetobacter baumannii. Based on the analysis of phenotypic and transcriptomic studies in vitro and in vivo, we propose that RND pumps of Gram-negative bacteria fall into three categories: constitutively expressed, regulated, and silent. These three categories of efflux pumps participate in different physiological programs, which are not involved in the central metabolism and bacterial growth.
细菌药物外排转运蛋白与细胞膜的扩散屏障和其他耐药机制协同作用，保护细胞免受抗生素和有毒代谢物的侵害。它们在临床抗生素和多药耐药性方面的关键作用已得到充分证实。此外，大量证据表明，它们在感染期间对细菌生长和增殖有重要贡献。然而，这些不同功能的药物转运蛋白如何在细菌细胞生理学水平上整合仍然不清楚。本文简要总结了目前对 ESKAPE 病原菌铜绿假单胞菌和鲍曼不动杆菌中抗性-结节-分裂（RND）超家族蛋白的药物外排泵的底物特异性和生理作用的理解。基于体外和体内表型和转录组学研究的分析，我们提出革兰氏阴性菌的 RND 泵可分为三类：组成型表达、调节型和沉默型。这三类外排泵参与不同的生理程序，不涉及中心代谢和细菌生长。
