School of Life Sciences, Hainan University, Haikou, China.
One Health Institute, Hainan University, Haikou, China.
Antimicrob Agents Chemother. 2023 Mar 16;67(3):e0096922. doi: 10.1128/aac.00969-22. Epub 2023 Feb 28.
Bacterial persisters refer to a small fraction of dormant variants that survive treatment with high concentrations of antibiotics. Increasing research indicates that multidrug efflux pumps play a major role in persister formation in many Gram-negative organisms. In the present study, the roles of the repressor of the AcrAB efflux pump, AcrR, in the regulation of the activity and function of the efflux, as well as in the production of persisters, were investigated in the pathogen Aeromonas veronii, which causes huge economic losses in the aquatic industry and threatens human health. We observed that exclusively in exponential-phase cells, not in stationary-phase cells, the deletion of the gene significantly ( < 0.05) promoted the expression of the and genes and reduced the intracellular accumulation of the efflux substrate Hoechst 33342. Moreover, overexpression of triggered decreased transcription of the promoter of the operon. The persister assay indicated that the loss of the AcrAB pump decreased the formation of persisters under challenge with all tested antibiotic types of chloramphenicol, fluoroquinolone, tetracycline, and β-lactam, while deletion of caused an exponential-phase-specific increase in persister formation against chloramphenicol, tetracycline, and β-lactam. Our results provide molecular insights into the mechanism of bacterial persistence by demonstrating for the first time that the local regulator AcrR is involved in the modulation of persister formation in through its repressive activity on the function of the AcrAB efflux pump during the exponential growth period.
细菌持久体是指一小部分休眠变体，它们能在高浓度抗生素的治疗下存活。越来越多的研究表明，多药外排泵在许多革兰氏阴性生物中持久体形成中起主要作用。在本研究中，研究了 AcrAB 外排泵的抑制剂 AcrR 在调节外排泵的活性和功能以及产生持久体方面的作用，在水生产业造成巨大经济损失并威胁人类健康的病原菌嗜水气单胞菌中。我们观察到，仅在指数生长期细胞中，而不在静止期细胞中， 基因的缺失显著（ < 0.05）促进了 和 基因的表达，并减少了流出底物 Hoechst 33342 的细胞内积累。此外， 过表达触发了 操纵子启动子转录的减少。持久体测定表明，在受到所有测试的抗生素类型（氯霉素、氟喹诺酮类、四环素和β-内酰胺类）的挑战下，AcrAB 泵的缺失减少了持久体的形成，而 的缺失导致氯霉素、四环素和β-内酰胺在指数生长期特异性地增加了持久体的形成。我们的结果提供了细菌持久性的分子机制的见解，首次证明局部调节剂 AcrR 通过其对 AcrAB 外排泵功能的抑制活性，在指数生长期间参与了 中持久体形成的调节。
