PA0833 is a novel virulence factor that contributes to the pathogenicity of Pseudomonas aeruginosa lung infection.

Pseudomonas aeruginosa (P. aeruginosa), a major cause of severe respiratory infections, particularly ventilator-associated pneumonia (VAP), employs various virulence mechanisms that remain incompletely characterized. In this study, we report that PA0833, an OmpA family outer membrane protein, acts as a novel virulence factor that is involved in the regulation of bacterial pathogenicity. We demonstrate that intranasal administration of recombinant PA0833 alone induces significant pulmonary inflammation in mice, characterized by alveolar disruption, neutrophil infiltration, and elevated pro-inflammatory cytokine levels in BALF, independent of live bacteria. Deletion of PA0833 attenuated virulence, reducing mortality, weight loss, lung inflammation, and tissue damage in P. aeruginosa infected mice, without affecting bacterial growth or colonization. Mechanistically, PA0833 triggered pro-inflammatory cytokine secretion in macrophages via TLR2-dependent activation of the NF-κB pathway, confirmed by TLR2 inhibition and co-immunoprecipitation. Furthermore, PA0833 deletion significantly impaired biofilm formation and reduced extracellular polysaccharide (EPS) content. This defect correlated with downregulation of key genes (mucA, mucB, algB, algD, algU) in the MucA-AlgU EPS biosynthesis pathway. Scanning electron microscopy revealed compromised cell wall integrity in the ΔPA0833 mutant. Collectively, our result indicates that PA0833 contributes to the virulence of P. aeruginosa, and targeting PA0833 offers a promising strategy for novel therapeutics against P. aeruginosa lung infections.