Department of Biomedical and Molecular Sciences, Botterell Hall, Queen's University, Kingston, ON, Canada.
PLoS One. 2018 Oct 5;13(10):e0205036. doi: 10.1371/journal.pone.0205036. eCollection 2018.
Exposure of P. aeruginosa to the aminoglycoside (AG) paromomycin (PAR) induced expression of the PA3720-armR locus and the mexAB-oprM multidrug efflux operon that AmgR controls, although PAR induction of mexAB-oprM was independent of armR. Multiple AGs promoted mexAB-oprM expression and this was lost in the absence of the amgRS locus encoding an aminoglycoside-activated envelope stress-responsive 2-component system (TCS). Purified AmgR bound to the mexAB-oprM promoter region consistent with this response regulator directly regulating expression of the efflux operon. The thiol-active reagent, diamide, which, like AGs, promotes protein aggregation and cytoplasmic membrane damage also promoted AmgRS-dependent mexAB-oprM expression, a clear indication that the MexAB-OprM efflux system is recruited in response to membrane perturbation and/or circumstances that lead to this. Despite the AG and diamide induction of mexAB-oprM, however, MexAB-OprM does not appear to contribute to resistance to these agents.
铜绿假单胞菌暴露于氨基糖苷（AG）巴龙霉素（PAR）会诱导 PA3720-armR 基因座和 MexAB-OprM 多药外排操纵子的表达，尽管 AmgR 控制的 PAR 诱导 MexAB-OprM 独立于 armR。多种 AG 促进了 mexAB-oprM 的表达，而在缺乏编码氨基糖苷激活的包膜应激反应 2 组分系统（TCS）的 amgRS 基因座的情况下，这种表达则丧失。纯化的 AmgR 与 mexAB-oprM 启动子区域结合，这与该反应调节剂直接调节外排操纵子的表达一致。硫醇活性试剂二酰胺，与 AG 一样，促进蛋白质聚集和细胞质膜损伤，也促进了 AmgRS 依赖性 mexAB-oprM 的表达，这清楚地表明 MexAB-OprM 外排系统是在响应膜扰动和/或导致这种情况的情况下被招募的。然而，尽管 AG 和二酰胺诱导了 mexAB-oprM，但 MexAB-OprM 似乎并没有对这些药物产生耐药性。
