Roles of Pseudomonas aeruginosa-derived proteases as a virulence factor

Abstract

The major virulence factors produced by Pseudomonas aeruginosa include secreted proteases that damage host tissues. Of the proteases analyzed, alkaline protease (AprA) and elastase B (LasB) have been characterized extensively. Although P. aeruginosa protein database predicts the presence of several other potential proteases, little has been known about the proteases involving in the pathogenicity of this organism. In this study, we found that P. aeruginosa produces a novel large extracellular protease (LepA) distinct from known proteases such as AprA and LasB. Sequence analysis of LepA showed a molecular future of the proteins transported by the two-partner secretion pathway. We demonstrated that LepA can activate NF-kB-driven promoter through protease-activated receptor-1, -2 or -4. On the other hand, one of the functions of proteases is to hydrolyze proteins and peptides for nutrient acquisition either by degrading host enzymes or even by causing tissue damage to further the survival of the bacterium. Therefore, to investigate the role of LepA in in vivo virulence and growth of P. aeruginosa, we compared the virulence and growth of a wild-type strain and its mutant using a mouse model of acute systemic infection by P. aeruginosa. Our results suggest that LepA contributes to the in vivo virulence and growth of P. aeruginosa.