Characterization of the role of global regulator FliA in the pathophysiology of Pseudomonas aeruginosa infection

Abstract

FliA is known to be a sigma factor that regulates bacterial flagella gene expression. Accumulating evidence suggests that FliA is involved in bacterial behavior other than motility. To elucidate the contribution of FliA to Pseudomonas aeruginosa pathophysiology, we analyzed the biological properties and gene expression profiles of a ΔfliA mutant. Transcriptome analysis results demonstrated that the expression levels of flagella biogenesis genes decreased dramatically in the mutant; consequently, the ΔfliA mutant failed to synthesize flagella and exhibited reduced motility. The ΔfliA mutant displayed stronger hemolytic and caseinolytic activities, as well as pyocyanin production. The expression of type 6 secretion system-II genes and interbacterial competition activity was decreased in the ΔfliA mutant. Direct evidence of fliA participation in virulence was obtained from analysis of hypervirulent strain B136-33. Adhesion to and cytotoxicity toward mammalian cells and penetration through cell layers were noted; furthermore, the colonization ability of the fliA::Tn5 mutant in the intestines of laboratory mice was compromised. Notably, the fliA-overexpressing strain displayed phenotypes similar to that of the fliA-defective strain, indicating that optimal FliA levels are critical to bacterial physiology. Our findings indicate that FliA plays diverse roles in P. aeruginosa, not only in flagella biosynthesis, but also in pathophysiology.