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类血小板的能力。牙龈假单胞菌具有高度的蛋白水解性，具有主要的保护酶、牙龈痛作用。牙周疼痛基因由N-末端蛋白水解区和C-末端粘附素结构域组成。Gingiain来源的粘附素Hgp44是P-gigivalis诱导人富含血小板血浆中的血小板聚集的关键分子。对截短的重组Hgp44蛋白的研究表明，其活性部位为N-末端(1-101aa)。该位点对Hgp44诱导的红细胞聚集也很重要。Hgp44可与人红细胞上的血糖素结合，也可与口腔上皮细胞结合。粘附素结构域也是牙龈痛抑制人口腔上皮细胞IL-8诱导的关键。核因子-Lib(RANKL)诱导的骨髓破骨细胞分化的受体激活剂被粘附素结构域HBr抑制。此外，牙龈痛影响细菌与宿主的相互作用，并可能直接促进细胞凋亡。我们确定了牙龈假单胞菌的模式菌株ATCC 33277的全基因组序列。这4个新基因是在33277菌株基因组上发现的，它们编码人参皂苷的粘附素结构域。这些基因失去了蛋白水解区。一些基因也被定义为将牙龈痛运输到细菌表面，并控制人参皂苷的表达。这些转运蛋白提示了人参皂苷的独特分泌系统。这些结果表明，牙痛来源的粘附素在宿主细胞中具有多种生物活性。这种复杂的活动可能有助于微生物在生态位上长期存在。显然，对Gigniain(也是其粘附素结构域蛋白)如何调节宿主细胞的详细了解将有助于揭示牙龈炎组织损伤的机制，并可能提供一种控制感染的药物方案。

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.