A novel secreted protease from Pseudomonas aeruginosa activates NF-κB through protease-activated receptors
A novel secreted protease from Pseudomonas aeruginosa activates NF-κB through protease-activated receptors
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DOI：
10.1111/j.1462-5822.2008.01142.x
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发表时间：
2008-07-01
影响因子：
3.4
通讯作者：
Kuwano, Koichi
中科院分区：
文献类型：
--
作者：
Kida, Yutaka;Higashimoto, Yuichiro;Kuwano, Koichi
铜绿假单胞菌衍生的碱性蛋白酶 (AprA)、弹性蛋白酶 A (LasA)、弹性蛋白酶 B (LasB) 和蛋白酶 IV 被认为在该生物体的发病机制中发挥重要作用。尽管铜绿假单胞菌基因组的序列分析预测基因组中存在编码其他潜在蛋白酶的多个基因，但人们对参与发病机制的蛋白酶知之甚少。最近，牙龈卟啉单胞菌 gingipains 和粘质沙雷氏菌 serralysin 已被证明可以激活蛋白酶激活受体 2 (PAR-2)，从而调节宿主炎症和免疫反应。因此，我们假设来自铜绿假单胞菌的未知蛋白酶也会通过 PAR 调节此类反应。在这项研究中，我们发现铜绿假单胞菌产生一种新型大蛋白酶 (LepA)，与 AprA、LasA、LasB 和蛋白酶 IV 等已知蛋白酶不同。 LepA 的序列分析显示了由两伙伴分泌途径转运的蛋白质的分子特征。我们的结果表明，LepA 通过人 PAR-1、-2 或 -4 激活 NF-κ B 驱动的启动子，并在特定位点裂解与人 PAR-1、-2 和 -4 的系留配体区域相对应的肽，并暴露其系留配体。综合考虑，这些结果表明 LepA 需要 PAR 来调节宿主针对细菌感染的各种反应。
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 protease (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-kappa B-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.