Roles of Porphyromonas gulae proteases in bacterial and host cell biology
Roles of Porphyromonas gulae proteases in bacterial and host cell biology
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DOI：
10.1111/cmi.13312
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发表时间：
2021-05-03
影响因子：
3.4
通讯作者：
Matsumoto-Nakano, Michiyo
中科院分区：
文献类型：
--
作者：
Urmi, Alam Saki;Inaba, Hiroaki;Matsumoto-Nakano, Michiyo
古氏卟啉单胞菌是一种动物来源的牙周病原体，它表达多种毒力因子，包括菌毛、脂多糖(LPS)和蛋白酶。我们以前报道过它的侵袭效率取决于菌毛的类型。此外，古氏肺孢子虫脂多糖通过Toll样受体增加炎症反应。本研究旨在探讨古氏肺孢子虫蛋白水解酶在细菌和宿主细胞生物学中的作用。古氏卟啉单胞菌表现出凝集小鼠红细胞的能力，并与粘性放线菌发生共聚集，而抗痛、PMSF、TLCK和亮肽素则降低了古氏卟啉单胞菌的蛋白分解活性，从而抑制了与粘性放线菌的血凝和共聚集。此外，还发现特定的蛋白水解酶抑制剂可以抑制细菌细胞的生长。古氏卟啉单胞菌以多种感染和时间依赖的方式抑制Ca9-22细胞的增殖。此外，P.guae诱导的细胞接触和黏附相关蛋白的减少伴随着细胞形态的显著变化，从均匀铺展到圆形。相反，抑制蛋白酶活性可以阻止E-钙粘蛋白、β-连环素和粘着斑激酶等蛋白质的降解，也可以阻止对细胞增殖的抑制。综上所述，这些结果表明古雷巴氏杆菌蛋白酶抑制了人类蛋白质的数量，如丙种球蛋白、纤维蛋白原和纤维连接蛋白，这表明一种新的蛋白酶复合体与细菌的毒力有关。
Porphyromonas gulae, an animal-derived periodontal pathogen, expresses several virulence factors, including fimbria, lipopolysaccharide (LPS) and proteases. We previously reported that its invasive efficiency was dependent on fimbriae types. In addition, P. gulae LPS increased inflammatory responses via toll-like receptors. The present study was conducted to investigate the involvement of P. gulae proteases in bacterial and host cell biology. Porphyromonas gulae strains showed an ability to agglutinate mouse erythrocytes and also demonstrated co-aggregation with Actinomyces viscosus, while the protease inhibitors antipain, PMSF, TLCK and leupeptin diminished P. gulae proteolytic activity, resulting in inhibition of haemagglutination and co-aggregation with A. viscosus. In addition, specific proteinase inhibitors were found to reduce bacterial cell growth. Porphyromonas gulae inhibited Ca9-22 cell proliferation in a multiplicity of infection- and time-dependent manner. Additionally, P. gulae-induced decreases in cell contact and adhesion-related proteins were accompanied by a marked change in cell morphology from well spread to rounded. In contrast, inhibition of protease activity prevented degradation of proteins, such as E-cadherin, beta-catenin and focal adhesion kinase, and also blocked inhibition of cell proliferation. Together, these results indicate suppression of the amount of human proteins, such as gamma-globulin, fibrinogen and fibronectin, by P. gulae proteases, suggesting that a novel protease complex contributes to bacterial virulence.