Zack Kira M, Sorenson Trent, Joshi Suresh G
Center for Surgical Infections and Biofilms, Department of Surgery, College of Medicine, Drexel University, Philadelphia, PA 19104, USA.
Center for Surgical Infections and Biofilms, Drexel School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, PA 19104, USA.
Pathogens. 2024 Feb 23;13(3):197. doi: 10.3390/pathogens13030197.
Bacteria express a plethora of efflux pumps that can transport structurally varied molecules, including antimicrobial agents and antibiotics, out of cells. Thus, efflux pump systems participate in lowering intracellular concentrations of antibiotics, which allows phenotypic multidrug-resistant (MDR) bacteria to survive effectively amid higher concentrations of antibiotics. is one of the classic examples of pathogens that can carry multiple efflux pump systems, which allows these bacteria to be MDR-to-pan-drug resistant and is now considered a public health threat. Therefore, efflux pumps in have gained major attention worldwide, and there has been increased interest in studying their mechanism of action, substrates, and potential efflux pump inhibitors (EPIs). Efflux pump inhibitors are molecules that can inhibit efflux pumps, rendering pathogens susceptible to antimicrobial agents, and are thus considered potential therapeutic agents for use in conjunction with antibiotics. This review focuses on the types of various efflux pumps detected in , their molecular mechanisms of action, the substrates they transport, and the challenges in developing EPIs that can be clinically useful in reference to .
细菌表达大量的外排泵,这些外排泵能够将结构多样的分子(包括抗微生物剂和抗生素)转运出细胞。因此,外排泵系统参与降低细胞内抗生素浓度,这使得表型多药耐药(MDR)细菌能够在较高浓度的抗生素环境中有效存活。是能够携带多种外排泵系统的病原体的经典例子之一,这使得这些细菌呈现多药耐药至泛耐药状态,目前被认为是一种公共卫生威胁。因此,中的外排泵已在全球范围内受到主要关注,并且对研究它们的作用机制、底物和潜在的外排泵抑制剂(EPI)的兴趣也在增加。外排泵抑制剂是能够抑制外排泵的分子,使病原体对抗微生物剂敏感,因此被认为是与抗生素联合使用的潜在治疗剂。本综述重点关注在中检测到的各种外排泵的类型、它们的分子作用机制、它们转运的底物以及开发对临床上参考有用的EPI所面临的挑战。