Phage-encoded protein PavP modulates Pseudomonas aeruginosa virulence by dual inhibition of growth and pathogenic traits.

Pseudomonas aeruginosa, one of the most prevalent pathogens, is notorious for its multidrug resistance, necessitating novel therapeutic strategies. Phage therapy has emerged as a promising alternative treatment strategy, which offers a dual advantage by directly killing bacteria and modulating host-pathogen interactions. Here, we identify PavP (PaoP5_160), a small protein encoded by bacteriophage PaoP5, which exhibits bacteriostatic activity on P. aeruginosa while altering virulence pathways at sub-inhibitory concentrations. Specifically, PavP impairs bacterial motility, enhances biofilm formation, and upregulates type 3 secretion system expression. The global transcriptome analysis shows that PavP modulates multiple pathways which participate in the pathogenicity and cell vitality of host bacteria. Crucially, in vivo virulence assays confirm that PavP attenuates P. aeruginosa pathogenicity. Our results reveal PavP as a multifunctional virulence modulator in P. aeruginosa, which highlights its potential as a dual-target antimicrobial agent capable of simultaneously restricting bacterial proliferation and disrupting virulence networks.