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Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of coxsackievirus and adenovirus receptor
Cellular Microbiology ( IF 2.6 ) Pub Date : 2021-08-27 , DOI: 10.1111/cmi.13388
Hiroki Takeuchi 1 , Shunsuke Yamaga 1 , Naoko Sasaki 2 , Masae Kuboniwa 1 , Michiya Matsusaki 2, 3 , Atsuo Amano 1
Affiliation  

Porphyromonas gingivalis is a major pathogen of human periodontitis and dysregulates innate immunity at the gingival epithelial surface. We previously reported that the bacterium specifically degrades junctional adhesion molecule 1 (JAM1), causing gingival epithelial barrier breakdown. However, the functions of other JAM family protein(s) in epithelial barrier dysregulation caused by P. gingivalis are not fully understood. The present results show that gingipains, Arg-specific or Lys-specific cysteine proteases produced by P. gingivalis, specifically degrade coxsackievirus and adenovirus receptor (CXADR), a JAM family protein, at R145 and K235 in gingival epithelial cells. In contrast, a gingipain-deficient P. gingivalis strain was found to be impaired in regard to degradation of CXADR. Furthermore, knockdown of CXADR in artificial gingival epithelium increased permeability to dextran 40 kDa, lipopolysaccharide and peptidoglycan, whereas overexpression of CXADR in a gingival epithelial tissue model prevented penetration by those agents following P. gingivalis infection. Together, these results suggest that P. gingivalis gingipains breach the stratified squamous epithelium barrier by degrading CXADR as well as JAM1, which allows for efficient transfer of bacterial virulence factors into subepithelial tissues.

中文翻译:

牙龈卟啉单胞菌通过降解柯萨奇病毒和腺病毒受体诱导脂多糖和肽聚糖穿过牙龈上皮细胞

牙龈卟啉单胞菌是人类牙周炎的主要病原体,会失调牙龈上皮表面的先天免疫。我们之前报道过这种细菌会特异性降解连接粘附分子 1 (JAM1),导致牙龈上皮屏障破坏。然而,其他果酱家族蛋白在由牙龈卟啉单胞菌引起的上皮屏障失调中的功能尚不完全清楚。目前的结果表明,牙龈卟啉单胞菌产生的 Arg 特异性或 Lys 特异性半胱氨酸蛋白酶在牙龈上皮细胞中的 R145 和 K235 处特异性降解柯萨奇病毒和腺病毒受体 (CXADR),一种 JAM 家族蛋白。相比之下,缺乏 gingipain 的P. gingivalis发现菌株在 CXADR 的降解方面受到损害。此外,在人工牙龈上皮中敲除 CXADR 会增加对 40 kDa 葡聚糖、脂多糖和肽聚糖的渗透性,而在牙龈上皮组织模型中过表达 CXADR 会阻止这些药物在牙龈卟啉单胞感染后的渗透。总之,这些结果表明P. gingivalis gingipains 通过降解 CXADR 和 JAM1 破坏了复层鳞状上皮屏障,这使得细菌毒力因子有效转移到上皮下组织中。
更新日期:2021-10-14
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