Role of O-specific antigen expression in Pseudomonas aeruginosa pathogenicity

Mbio, Page e0155126

Pseudomonas aeruginosa is a versatile, opportunistic pathogen, well-known for its adaptability to the challenging conditions encountered during infection of the human host. In chronic biofilm-associated infections, variations in motility and LPS structure are commonly observed adaptive traits. In this study, we identified differences in the expression of the O-specific antigen (OSA) biosynthetic cluster as a key driver of motility variation among a large number of clinical PA14 clade isolates. Despite retaining flagellar presence and function, OSA-deficient mutants exhibited increased hydrophobicity, which enhanced surface attachment and, in turn, reduced surface motility while promoting biofilm formation. The modified lipopolysaccharide structure with a lack of OSA also resulted in increased serum sensitivity, reduced phagocytic uptake, increased aminoglycoside resistance, and enhanced expression of the type III secretion system. These findings suggest that the commonly observed loss of OSA in P. aeruginosa isolates recovered from chronically infected cystic fibrosis lungs may be selectively advantageous. Importantly, we demonstrate that clinically relevant phenotypes influenced by the presence of OSA, such as motility and antibiotic resistance, become detectable only under test conditions that promote bacterial attachment. Similarly, the role of OSA expression in bacterial pathogenicity is conditional, with neither its presence nor its absence uniformly favoring infection. Together, our findings support a model in which OSA expression may be beneficial during early infection, whereas reduced OSA expression may promote traits associated with persistence at later stages.IMPORTANCELoss of the O-specific antigens (OSA) in Pseudomonas aeruginosa isolates recovered from chronically infected cystic fibrosis lungs is a commonly observed phenotype that may confer a selective advantage to this opportunistic pathogen. In this study, we demonstrate that P. aeruginosa strains lacking OSA become more adhesive, limiting their motility but enhancing biofilm formation. Furthermore, OSA-deficient strains exhibit increased serum sensitivity, while they are phagocytosed less, express elevated type III secretion system genes, and show enhanced antibiotic resistance. Our findings suggest that altered OSA expression may contribute to stage-dependent infection phenotypes, where reduced OSA expression during later stages drives biofilm formation and antibiotic resistance, thereby enabling persistence.

DOI: 10.1128/mbio.01551-26