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

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

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1491-1504
Number of pages14
JournalCellular Microbiology
Volume10
Issue number7
DOIs
Publication statusPublished - 2008 Jul
Externally publishedYes

Fingerprint

Exopeptidases
Proteinase-Activated Receptors
Peptide Hydrolases
serralysin
Pancreatic Elastase
Pseudomonas aeruginosa
Sequence Analysis
Genes
PAR-2 Receptor
Genome
Ligands
Porphyromonas gingivalis
Serratia marcescens
Gene encoding
Secretory Pathway
Bacterial Infections
Peptides
Pseudomonas serine proteinase
Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

A novel secreted protease from Pseudomonas aeruginosa activates NF-KB through protease-activated receptors. / Kida, Yutaka; Higashimoto, Yuichiro; Inoue, Hiroyoshi; Shimizu, Takashi; Kuwano, Koichi.

In: Cellular Microbiology, Vol. 10, No. 7, 07.2008, p. 1491-1504.

Research output: Contribution to journalArticle

Kida, Yutaka ; Higashimoto, Yuichiro ; Inoue, Hiroyoshi ; Shimizu, Takashi ; Kuwano, Koichi. / A novel secreted protease from Pseudomonas aeruginosa activates NF-KB through protease-activated receptors. In: Cellular Microbiology. 2008 ; Vol. 10, No. 7. pp. 1491-1504.
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