Comparative analysis of five type II TA systems identified in Pseudomonas aeruginosa reveals their contributions to persistence and intracellular survival

BackgroundPseudomonas aeruginosa is a grave nosocomial pathogen that persistently inhabits the lungs of patients with cystic fibrosis (CF) and causes various chronic infections. The bacterial toxin-antitoxin (TA) system is associated with latent and long-term infections, but the underlying mechanisms remain to be fully characterized. MethodsWe here investigated the diversity and function of five genomic type II TA systems widely distributed among P. aeruginosa clinical isolates. We also examined the distinct structural features of the toxin protein from different TA systems and characterized their contributions to persistence, invasion ability, and intracellular infection caused by P. aeruginosa. ResultsParDE, PA1030/PA1029, and HigBA could modulate persister cell formation under treatment with specific antibiotics. Furthermore, cell-based transcriptional and invasion assays revealed that PA1030/PA1029 and HigBA TA systems were critical for intracellular survival. DiscussionOur results highlight the prevalence and diverse roles of type II TA systems in P. aeruginosa and evaluate the possibility of using PA1030/PA1029 and HigBA TA pairs as targets for novel antibiotic treatments.

Automated summary

This study investigated the diversity and function of five genomic type II TA systems in Pseudomonas aeruginosa clinical isolates and their impact on the persistence and invasion ability of the bacteria. The PA1030/PA1029 and HigBA TA systems were found to be critical for intracellular survival and could be potential targets for novel antibiotic treatments.