Study for gignipain-related adhesins of Periodontal pathogen, Porphyromonas gingivalis for its platelet aggregation activity

牙周病原体牙龈卟啉单胞菌具有聚集人血小板的能力。牙龈卟啉卟啉是高度蛋白水解的，具有主要的蛋白酶，牙龈蛋白酶。牙龈蛋白酶基因由n端蛋白水解结构域和c端黏附蛋白结构域组成。龈蛋白酶衍生黏附素Hgp44是人富血小板血浆中龈蛋白酶诱导血小板聚集的关键分子。截断重组Hgp44蛋白的研究表明，活性位点为n端部分（1-101 aa）。该位点对hgp44诱导的红细胞聚集也很重要。Hgp44与人红细胞上的糖蛋白结合，也与人口腔上皮细胞结合。黏附素结构域也是牙龈痛抑制人口腔上皮细胞诱导IL-8的关键。核因子- lib （RANKL）诱导的骨髓破骨细胞发生受体激活因子被粘附素结构域之一HbR抑制。此外，牙龈疼痛影响细菌与宿主的相互作用，并可能直接促进细胞凋亡。我们确定了牙龈P型菌株ATCC 33277的全基因组序列。在ATCC 33277基因组上发现了编码木质素粘附素结构域的4个新基因。这些基因失去了蛋白水解结构域。还确定了一些将牙龈蛋白酶转运到细菌表面并控制牙龈蛋白酶表达的基因。这些转运蛋白提示木质素的独特分泌系统。这些结果表明，牙龈蛋白酶衍生的黏附素在宿主细胞中具有多种生物活性。这种复杂的活性可能有助于微生物在生态位中长期存在。显然，对木质素及其粘附结构域蛋白如何调节宿主细胞的详细了解，将为研究牙龈炎组织损伤的机制提供重要线索，并可能提供控制感染的药理学方案。

The periodontal pathogen Porphyromonas gingivalis has the ability to aggregate human platelets. P. gingivalis is highly proteolytic, has major protainases, gingipains. The gingipain genes are consisting of N-terminal proteolytic domain and C-terminal adhesin domains. Gingipain derived adhesin, Hgp44 is the key molecule for P gingivalis-induced platelet aggregation in human platelet-rich plasma. The study of truncated recombinant Hgp44 protein shows that the active site is the N-terminal part (1-101 aa). This site is also important for Hgp44-induced erythrocyte aggregation. Hgp44 binds to glycophorin on human erythrocyte, also to human oral epithelial cells. The adhesin domains are also essential for gingipains to suppress of IL-8 induction from human oral epithelial cells. The receptor activator of nuclear factor-LIB (RANKL)-induced osteoclastogenesis from bone marrow is inhibited by one of adhesin domain, HbR. Furthermore the gingipains affect bacteria-host interactions and may directly promote apoptosis. We defined the complete genome sequence of strain ATCC 33277 that is the type strain of P gingivalis. The newly 4 genes find on genome of ATCC 33277 that encoded the adhesin domains of gignipains. Those genes lost the proteolytic domains. Some genes are also defined that transports gingipain to bacterial surface and controls expression of gignipains. Those transporters suggested the unique secretion system for gignipain. Those results indicates that gingipain derived adhesins has various biological activity in host cells. Such complex activity might to help the microorganism exist long in the niche. Clearly, a detailed knowledge of how gignipain, also its adhesin domain protein, regulates host cells will shed important light on the mechanism of tissue damage in gingivitis and may provide a pharmacological regimen to control the infection.