Journal
INFECTION AND DRUG RESISTANCE
Volume 15, Issue -, Pages 4213-4227Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IDR.S371597
Keywords
Pseudomonas aeruginosa; PtrA; T3SS; Quorum-sensing; pathogenicity; carbapenems resistance
Categories
Funding
- Zhejiang Province Natural Science Foundation of China [LY18H190004]
- Health Department of Zhejiang Province of the People?s Republic of China [2018KY123]
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This study reveals that PtrA plays a dual regulatory role in the virulence systems of Pseudomonas aeruginosa, negatively regulating the T3SS and positively regulating the QS. The absence of ptrA leads to a weakened extracellular virulence related to QS and affects the carbapenems resistance of PA.
Introduction: Globally, Pseudomonas aeruginosa (PA) is emerging as a predominant nosocomial pathogen that often induces aggressive and even deadly infections. Pseudomonas type III repressor A (PtrA) can be activated specifically by copper ions and interacts with type-III transcriptional activator ExsA. This study aims to provide insight into the PtrA-mediated regulation of the pathogenicity and antibiotics resistance of PA.Methods and Results: The results of transcriptome sequencing analyses and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) showed that PtrA plays a dual regulatory role in the virulence systems of PA: negatively regulates the type-III secretion system (T3SS) and positively regulates the quorum-sensing system (QS). The ptrA mutant attenuated extracellular virulence related to QS like pyocyanin, elastase, rhamnolipids, proteolytic activity, and biofilm production. According to adhesion and invasion experiments, PtrA can not only contribute to the adhesiveness but also the invasive of PA. Moreover, the PtrA-mediated regulation of PA pathogenicity was determined both in vivo and in vitro through cytotoxicity and Galleria mellonella survival experiments. In addition, apart from virulence, PtrA was found to influence the carbapenems resistance of PA. After deleting ptrA , the minimum inhibitory concentration (MIC) of carbapenems antibiotics was decreased by 2-fold, while a 2-8 fold increase was noted for the complemented strain.Conclusion: Our findings establish that PtrA exerts a regulatory role in both pathogenicity and carbapenems resistance of PA. This work may shed light on a novel target for the clinical treatment of PA.
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