A novel secreted protease from Pseudomonas aeruginosa activates NF-kappaB through protease-activated receptors
| Project/Area Number |
20790343
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kurume University |
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Principal Investigator |
KIDA Yutaka Kurume University, 医学部, 助教 (30309752)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | プロテアーゼ / プロテアーゼ活性化受容体 / 緑膿菌 / V型分泌装置 |
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| Research 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-kappaB-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.
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Report
(3 results)
Research Products
(7 results)
