A novel secreted protease from Pseudomonas aeruginosa activates NF-KB through protease-activated receptors

Yutaka Kida, Yuichiro Higashimoto, Hiroyoshi Inoue, Takashi Shimizu, Koichi Kuwano

研究成果: Article査読

83 被引用数 (Scopus)

抄録

The Pseudomonas aeruginosa -derived alkaline protease (AprA), elastase A (LasA), elastase B (LasB) and protease IV are considered to play an important role in pathogenesis of this organism. Although the sequence analysis of P.aeruginosa genome predicts the presence of several genes encoding other potential proteases in the genome, little has been known about the proteases involving in pathogenesis. Recently, Porphyromonas gingivalis gingipains and Serratia marcescens serralysin have been shown to activate protease-activated receptor 2 (PAR-2), thereby modulating host inflammatory and immune responses. Accordingly, we hypothesized that unknown protease(s) from P. aeruginosa would also modulate such responses through PARs. In this study, we found that P. aeruginosa produces a novel large exoprotease (LepA) distinct from known proteases such as AprA, LasA, LasB and protease IV. Sequence analysis of LepA showed a molecular feature of the proteins transported by the two-partner secretion pathway. Our results indicated that LepA activates NF-κB-driven promoter through human PAR-1, -2 or -4 and cleaves the peptides corresponding to the tethered ligand region of human PAR-1, -2 and -4 at a specific site with exposure of their tethered ligands. Considered together, these results suggest that LepA would require PARs to modulate various host responses against bacterial infection.

本文言語English
ページ(範囲)1491-1504
ページ数14
ジャーナルCellular Microbiology
10
7
DOI
出版ステータスPublished - 2008 7月
外部発表はい

ASJC Scopus subject areas

  • 微生物学
  • 免疫学
  • ウイルス学

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