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Pseudomonas aeruginosa Polynucleotide Phosphorylase Controls Tolerance to Aminoglycoside Antibiotics by Regulating the MexXY Multidrug Efflux Pump
Antimicrobial Agents and Chemotherapy ( IF 4.9 ) Pub Date : 2021-01-20 , DOI: 10.1128/aac.01846-20
Zheng Fan 1 , Xiaolei Pan 1 , Dan Wang 1 , Ronghao Chen 1 , Tongtong Fu 1 , Baopeng Yang 1 , Yongxin Jin 1 , Fang Bai 1 , Zhihui Cheng 1 , Weihui Wu 2
Affiliation  

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.

中文翻译:

铜绿假单胞菌多核苷酸磷酸化酶通过调节MexXY多药外排泵控制对氨基糖苷类抗生素的耐受性

铜绿假单胞菌是一种机会病原体,对多种抗生素表现出很高的内在抗性。MexX-MexY-OprM外排泵在细菌对氨基糖苷类抗生素的耐药性中起重要作用。多核苷酸磷酸化酶(PNPase)是高度保守的核酸外切酶,在RNA加工和细菌对环境压力的反应中起重要作用。以前,我们证明了PNPase通过影响铜绿假单胞菌中的霉素生成来控制对氟喹诺酮类抗生素的耐受性。在这项研究中,我们发现铜绿假单胞菌中PNPase编码基因(pnp)的突变增加了细菌对氨基糖苷类抗生素的耐受性。我们进一步证明,mexXY基因负责增强pnp突变体的耐受性。此外,我们的实验结果表明,PNPase通过其5'非翻译区(UTR)控制armZ mRNA的翻译。ArmZ先前已被证明可以积极调节mexXY的表达。因此,我们的研究结果揭示了PNPase在armZ和随后的MexXY外排泵调节中的新作用。
更新日期:2021-01-20
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