Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 1, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01166-20
Keywords
MexXY; aminoglycoside resistance; aminoglycoside-modifying enzymes; antibiotic efflux; antibiotic resistance
Categories
Funding
- European Union (ERC) [COMBAT 724290]
- Deutsche Forschungsgemeinschaft (DFG
- German Research Foundation) under Germany's Excellence Strategy [EXC 2155, 39087428]
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Elevated mexXY gene expression levels in clinical Pseudomonas aeruginosa isolates result in slight increases in aminoglycoside MIC levels, but rarely lead to clinically relevant resistance phenotypes. The main driver of resistance in these clinical isolates is the acquisition of aminoglycoside-modifying enzymes (AMEs), which is strongly associated with mexY overexpression. The introduction of a gentamicin acetyltransferase confers full resistance levels in a P. aeruginosa type strain only if the MexXY efflux pump is active.
The impact of MexXY efflux pump expression on aminoglycoside resistance in clinical Pseudomonas aeruginosa isolates has been debated. In this study, we found that, in general, elevated mexXY gene expression levels in clinical P. aeruginosa 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 mexY overexpression. In line with this observation, we demonstrate that the introduction of a gentamicin acetyltransferase confers to full gentamicin resistance levels in a P. aeruginosa type strain only if the MexXY efflux pump was active. We discuss that increased mexXY activity in clinical AME-harboring P. aeruginosa 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.
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