Local Regulator AcrR Regulates Persister Formation by Repression of AcrAB Efflux Pump during Exponential Growth in Aeromonas veronii
Local Regulator AcrR Regulates Persister Formation by Repression of AcrAB Efflux Pump during Exponential Growth in Aeromonas veronii
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DOI：
10.1128/aac.00969-22
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发表时间：
2023-02
影响因子：
4.9
通讯作者：
Xiang Ma;K. Hu;Yuesheng Xiong;Hong Li;Juanjuan Li;Yanqiong Tang;Zhu Liu
中科院分区：
文献类型：
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作者：
Xiang Ma;K. Hu;Yuesheng Xiong;Hong Li;Juanjuan Li;Yanqiong Tang;Zhu Liu
细菌持续存在是指一小部分休眠变种，在高浓度抗生素治疗后仍能存活。越来越多的研究表明，多药外排泵在许多革兰氏阴性菌中持续存在的形成中起着重要作用。摘要细菌持久性是指一小部分在高浓度抗生素治疗后仍能存活的休眠变体。越来越多的研究表明，多药外排泵在许多革兰氏阴性菌中持续存在的形成中起着重要作用。本研究探讨了在水产养殖业造成巨大经济损失并威胁人类健康的病原菌Veronii中AcrAB外排泵阻遏物AcrR对外排泵活性和功能的调节以及在持久性芽孢杆菌产生中的作用。我们观察到，仅在指数期细胞，而不是在静止期细胞，acrR基因的缺失显着（P < 0.05）促进acrA和acrB基因的表达，减少细胞内积累的外排底物Hoechst 33342。此外，acrR的过表达触发acrAB操纵子的启动子的转录降低。持续存在试验表明，AcrAB泵的缺失减少了氯霉素、氟喹诺酮、四环素和β-内酰胺等所有测试抗生素类型挑战下持续存在菌的形成，而acrR缺失导致氯霉素、四环素和β-内酰胺的持续存在菌形成呈指数阶段特异性增加。我们的研究结果首次证明了局部调节因子AcrR参与了A. veronii通过其对指数生长期AcrAB外排泵功能的抑制活性。
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. ABSTRACT 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 acrR gene significantly (P < 0.05) promoted the expression of the acrA and acrB genes and reduced the intracellular accumulation of the efflux substrate Hoechst 33342. Moreover, overexpression of acrR triggered decreased transcription of the promoter of the acrAB 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 acrR 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 A. veronii through its repressive activity on the function of the AcrAB efflux pump during the exponential growth period.