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

Ying Zhang; Lingbo Wang; Liqiong Chen; Peiwu Zhu; Na Huang; Tao Chen; Lijiang Chen; Zhongyong Wang; Wenli Liao; Jianming Cao; Tieli Zhou

doi:10.2147/IDR.S371597

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

Infect Drug Resist. 2022 Aug 4:15:4213-4227. doi: 10.2147/IDR.S371597. eCollection 2022.

Authors

Ying Zhang^#¹, Lingbo Wang^#¹, Liqiong Chen², Peiwu Zhu¹, Na Huang¹, Tao Chen¹, Lijiang Chen¹, Zhongyong Wang¹, Wenli Liao¹, Jianming Cao², Tieli Zhou¹

Affiliations

¹ Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, People's Republic of China.
² Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, People's Republic of China.

^# Contributed equally.

Abstract

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.

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

Grants and funding

This work was supported by the Zhejiang Province Natural Science Foundation of China [grant numbers LY18H190004]; the Health Department of Zhejiang Province of the People’s Republic of China [grant numbers 2018KY123].