Pseudomonas aeruginosa Polynucleotide Phosphorylase Controls Tolerance to Aminoglycoside Antibiotics by Regulating the MexXY Multidrug Efflux Pump

Abstract

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that shows high intrinsic resistance to a variety of antibiotics. The MexX-MexY-OprM efflux pump plays an important role in bacterial resistance to aminoglycoside antibiotics. Polynucleotide phosphorylase (PNPase) is a highly conserved exonuclease that plays important roles in RNA processing and the bacterial response to environmental stresses. Previously, we demonstrated that PNPase controls the tolerance to fluoroquinolone antibiotics by influencing the production of pyocin in P. aeruginosa. In this study, we found that mutation of the PNPase-encoding gene (pnp) in P. aeruginosa increases bacterial tolerance to aminoglycoside antibiotics. We further demonstrate that the upregulation of the mexXY genes is responsible for the increased tolerance of the pnp mutant. Furthermore, our experimental results revealed that PNPase controls the translation of the armZ mRNA through its 5′ untranslated region (UTR). ArmZ had previously been shown to positively regulate the expression of mexXY. Therefore, our results revealed a novel role of PNPase in the regulation of armZ and subsequently the MexXY efflux pump.