Atypical toxin psyrT modulates bacterial virulence and host inflammatory responses in Pseudomonas...

Bacterial toxin-antitoxin (TA) systems are widespread genetic modules that regulate bacterial stress adaptation and pathogenicity. The atypical Type II psyrTA system encodes the toxin PsyrT with conserved RecQ-containing DEXDc and HELICc helicase domains, a rare architecture among characterized TA toxins. The toxic and pathogenic regulatory functions of helicase-containing TA toxins remain experimentally unvalidated. Here, we functionally characterized the psyrTA system in Pseudomonas plecoglossicida PQLYC4, the pathogen causing visceral white spot disease in large yellow croaker. Heterologous expression in Escherichia coli verified that PsyrT exerts potent growth-inhibitory toxicity, which is efficiently alleviated by cognate PsyrA via direct physical interaction. Deletion of psyrT markedly impaired biofilm formation, downregulated virulence gene transcription, reduced splenic colonization, and alleviated splenic histopathological damage in infected fish. Additionally, ΔpsyrT infection significantly attenuated host splenic cytokine transcriptional responses. Collectively, this study identifies PsyrT as a novel RecQ helicase domain-containing TA toxin and an important virulence modulator in P. plecoglossicida, expanding the functional diversity of bacterial TA systems.