Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of coxsackievirus and adenovirus receptor

IF 2.6 2区生物学 Q3 CELL BIOLOGY

Cellular Microbiology Pub Date : 2021-08-27 DOI:10.1111/cmi.13388

Hiroki Takeuchi, Shunsuke Yamaga, Naoko Sasaki, Masae Kuboniwa, Michiya Matsusaki, Atsuo Amano

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引用次数: 6

Abstract

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.

Takeaways

P. gingivalis, a periodontal pathogen, degraded coxsackievirus and adenovirus receptor (CXADR), a JAM family protein, in gingival epithelial tissues.
P. gingivalis gingipains, cysteine proteases, degraded CXADR at R145 and K235.
CXADR degradation by P. gingivalis caused increased permeability to lipopolysaccharide and peptidoglycan through gingival epithelial tissues.

Abstract Image

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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渗透牙龈上皮

牙龈卟啉单胞菌是人类牙周炎的一种主要病原体，它能失调牙龈上皮表面的先天免疫。我们之前报道过这种细菌特异性地降解连接粘附分子1 (JAM1)，导致牙龈上皮屏障破裂。然而，其他JAM家族蛋白在牙龈卟啉卟啉引起的上皮屏障失调中的功能尚不完全清楚。本研究结果表明，牙龈卟啉卟啉产生的arg特异性或lys特异性半胱氨酸蛋白酶gingipains可特异性降解牙龈上皮细胞中位于R145和K235位点的柯萨奇病毒和腺病毒受体(CXADR)家族蛋白。相比之下，缺乏牙龈蛋白酶的牙龈卟啉卟啉菌株在CXADR的降解方面受到损害。此外，在人工牙龈上皮中，CXADR的低表达增加了对40 kDa葡聚糖、脂多糖和肽聚糖的通透性，而在牙龈上皮组织模型中，CXADR的过表达阻止了牙龈假单胞菌感染后这些物质的渗透。总之，这些结果表明，牙龈卟啉卟啉菌通过降解CXADR和JAM1来破坏分层鳞状上皮屏障，从而允许细菌毒力因子有效地转移到上皮下组织。牙龈卟啉卟啉(P. gingivalis)是一种牙周病原体，可降解牙龈上皮组织中的柯萨奇病毒和腺病毒受体(CXADR)。P. gingivalis gingipains，半胱氨酸蛋白酶，在R145和K235位点降解CXADR。牙龈卟啉单胞菌降解CXADR导致脂多糖和肽聚糖通过牙龈上皮组织的通透性增加。

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来源期刊

Cellular Microbiology 生物-微生物学

CiteScore

9.70

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.