Department of Discovery Biology, Antibacterial Resistance Laboratory, Institut Pasteur Korea, Seongnam 13488, Korea.
BMB Rep. 2023 Jun;56(6):326-334. doi: 10.5483/BMBRep.2023-0070.
Antibiotic resistance (AR) is a silent pandemic that kills millions worldwide. Although the development of new therapeutic agents against antibiotic resistance is in urgent demand, this has presented a great challenge, especially for Gram-negative bacteria that have inherent drug-resistance mediated by impermeable outer membranes and multidrug efflux pumps that actively extrude various drugs from the bacteria. For the last two decades, multidrug efflux pumps, including AcrAB-TolC, the most clinically important efflux pump in Gram-negative bacteria, have drawn great attention as strategic targets for re-sensitizing bacteria to the existing antibiotics. This article aims to provide a concise overview of the AcrAB-TolC operational mechanism, reviewing its architecture and substrate specificity, as well as the recent development of AcrAB-TolC inhibitors. [BMB Reports 2023; 56(6): 326-334].
抗生素耐药性（AR）是一场无声的大流行，在全球范围内导致数百万人死亡。尽管急需开发针对抗生素耐药性的新治疗药物，但这带来了巨大的挑战，尤其是对于革兰氏阴性菌而言，其固有耐药性是由不可渗透的外膜和多种药物外排泵介导的，这些外排泵可主动将各种药物从细菌中排出。在过去的二十年中，包括 AcrAB-TolC 在内的多种药物外排泵已引起人们的极大关注，因为它们是重新使细菌对现有抗生素敏感的战略靶标，而 AcrAB-TolC 是革兰氏阴性菌中最重要的临床外排泵。本文旨在简要概述 AcrAB-TolC 的作用机制，综述其结构和底物特异性，以及 AcrAB-TolC 抑制剂的最新研究进展。[BMB 报告 2023; 56(6): 326-334]。
