Novel Insight of Transcription Factor PtrA on Pathogenicity and Carbapenems Resistance in Pseudomonos aeruginosa

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-Ill 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-Ill 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. Keywords: Pseudomonas aeruginosa, PtrA, T3SS, Quorum-sensing, pathogenicity, carbapenems resistance