Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Department of Molecular Bacteriology, Twincore, Hannover, Germany.
Antimicrob Agents Chemother. 2020 Dec 16;65(1). doi: 10.1128/AAC.01166-20.
The impact of MexXY efflux pump expression on aminoglycoside resistance in clinical isolates has been debated. In this study, we found that, in general, elevated gene expression levels in clinical isolates confer to slight increases in aminoglycoside MIC levels; however, those levels rarely lead to clinically relevant resistance phenotypes. The main driver of resistance in the clinical isolates studied here was the acquisition of aminoglycoside-modifying enzymes (AMEs). Nevertheless, acquisition of an AME was strongly associated with overexpression. In line with this observation, we demonstrate that the introduction of a gentamicin acetyltransferase confers to full gentamicin resistance levels in a type strain only if the MexXY efflux pump was active. We discuss that increased activity in clinical AME-harboring isolates might affect ion fluxes at the bacterial cell membrane and thus might play a role in the establishment of enhanced fitness that extends beyond aminoglycoside resistance.
MexXY 外排泵表达对临床分离株中氨基糖苷类耐药性的影响一直存在争议。在本研究中，我们发现，一般来说，临床分离株中基因表达水平的升高仅导致氨基糖苷类 MIC 水平的轻微升高；然而，这些水平很少导致临床上相关的耐药表型。这里研究的临床分离株中耐药的主要驱动因素是获得氨基糖苷类修饰酶（AMEs）。然而，AME 的获得与过度表达强烈相关。与这一观察结果一致，我们证明，只有在 MexXY 外排泵活跃的情况下，引入庆大霉素乙酰转移酶才能使 型菌株完全对庆大霉素产生耐药性。我们讨论了在临床携带 AME 的分离株中增加的活性可能会影响细菌细胞膜的离子通量，因此可能在建立增强的适应性方面发挥作用，这种适应性超出了氨基糖苷类耐药性。
