Ding Yinhuan, Hao Jingchen, Xiao Weijia, Ye Caihong, Xiao Xue, Jian Chunxia, Tang Min, Li Guangrong, Liu Jinbo, Zeng Zhangrui
Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
Front Microbiol. 2023 Aug 4;14:1207441. doi: 10.3389/fmicb.2023.1207441. eCollection 2023.
Colistin is highly promising against multidrug-resistant and extensively drug-resistant bacteria clinically. Bacteria are resistant to colistin mainly through and chromosome-mediated lipopolysaccharide (LPS) synthesis-related locus variation. However, the current understanding cannot fully explain the resistance mechanism in -negative colistin-resistant strains. Significantly, the contribution of efflux pumps to colistin resistance remains to be clarified. This review aims to discuss the contribution of efflux pumps and their related transcriptional regulators to colistin resistance in various bacteria and the reversal effect of efflux pump inhibitors on colistin resistance. Previous studies suggested a complex regulatory relationship between the efflux pumps and their transcriptional regulators and LPS synthesis, transport, and modification. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), 1-(1-naphthylmethyl)-piperazine (NMP), and Phe-Arg-β-naphthylamide (PAβN) all achieved the reversal of colistin resistance, highlighting the role of efflux pumps in colistin resistance and their potential for adjuvant development. The contribution of the efflux pumps to colistin resistance might also be related to specific genetic backgrounds. They can participate in colistin tolerance and heterogeneous resistance to affect the treatment efficacy of colistin. These findings help understand the development of resistance in -negative colistin-resistant strains.
多黏菌素在临床上对多重耐药菌和广泛耐药菌具有很大的应用前景。细菌对多黏菌素的耐药主要通过质粒和染色体介导的脂多糖（LPS）合成相关位点变异。然而，目前的认识尚不能完全解释革兰氏阴性多黏菌素耐药菌株的耐药机制。值得注意的是，外排泵对多黏菌素耐药性的作用仍有待阐明。本综述旨在探讨外排泵及其相关转录调节因子对不同细菌中多黏菌素耐药性的作用以及外排泵抑制剂对多黏菌素耐药性的逆转作用。先前的研究表明外排泵与其转录调节因子以及LPS合成、转运和修饰之间存在复杂的调控关系。羰基氰3-氯苯腙（CCCP）、1-（1-萘甲基）哌嗪（NMP）和苯丙氨酸-精氨酸-β-萘酰胺（PAβN）均实现了对多黏菌素耐药性的逆转，突出了外排泵在多黏菌素耐药性中的作用及其作为佐剂开发的潜力。外排泵对多黏菌素耐药性的作用可能还与特定的遗传背景有关。它们可参与多黏菌素耐受性和异质性耐药，从而影响多黏菌素的治疗效果。这些发现有助于了解革兰氏阴性多黏菌素耐药菌株的耐药发展情况。
