Clathrin-dependent entry of a gingipain adhesin peptide and<i>Porphyromonas gingivalis</i>into host cells

Boisvert, Heike; Duncan, Marilyn J.

doi:10.1111/j.1462-5822.2008.01228.x

Cited by 28 publications

(41 citation statements)

References 60 publications

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“…gingivalis pathogenicity and more recently for their role in cell invasion (Boisvert & Duncan, 2008;Fitzpatrick et al, 2009;Chen & Duncan, 2004). In light of their importance in this process we decided to examine whether the levels of these proteases might be altered in the invasive and noninvasive subtypes compared with isogenic wild-type strains.…”

Section: Stability Of the Invasive Phenotypementioning

confidence: 99%

Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion

et al. 2010

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Bistable populations of bacteria give rise to two or more subtypes that exhibit different phenotypes. We have explored whether the periodontal pathogen Porphyromonas gingivalis exhibits bistable invasive phenotypes. Using a modified cell invasion assay, we show for the first time that there are two distinct subtypes within a population of P. gingivalis strains NCTC 11834 and W50 that display differences in their ability to invade oral epithelial cells. The highly invasive subtype invades cells at 10-30-fold higher levels than the poorly invasive subtype and remains highly invasive for approximately 12-16 generations. Analysis of the gingipain activity of these subtypes revealed that the highly invasive type had reduced cell-associated arginine-specific protease activity. The role of Arg-gingipain activity in invasion was verified by enhancement of invasion by rgpAB mutations and by inclusion of an Arg-gingipain inhibitor in invasion assays using wild-type bacteria. In addition, a population of DrgpAB bacteria did not contain a hyperinvasive subtype. Screening of the protease activity of wild-type populations of both strains identified high and low protease subtypes which also showed a corresponding reduction or enhancement, respectively, of invasive capabilities. Microarray analysis of these bistable populations revealed a putative signature set of genes that includes oxidative stress resistance and iron transport genes, and which might be critical to invasion of or survival within epithelial cells.

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Section: Stability Of the Invasive Phenotypementioning

confidence: 99%

Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion

et al. 2010

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“…It is known that the gingipain adhesin fragment A44 binds to and is internalized by HEp-2 cells in a dose-and time-dependent manner (17). Moreover, A44 can directly bind to host FN (7). To identify potentially novel binding partners, protein capture with the use of A44 as bait was performed (Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

“…Binding partners for fimbriae include fibronectin (FN) and its cognate receptor α5β1 integrin (5,6,(10)(11)(12). The adhesin domains of arg-gingipain A and lys-gingipain were shown to bind to epithelial cells, and the adhesin peptide A44 of the former has a high affinity for host FN (7,13). In addition to integrins and ECM proteins, P. gingivalis interacts with several other receptors (14)(15)(16).…”

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confidence: 99%

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Transglutaminase 2 is essential for adherence of Porphyromonas gingivalis to host cells

Boisvert¹,

Lóránd

Duncan³

2014

Proc. Natl. Acad. Sci. U.S.A.

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Porphyromonas gingivalis is the major causative agent of periodontitis, and it may also be involved in the development of systemic diseases (atherosclerosis, rheumatoid arthritis). P. gingivalis is found on and within oral and gingival epithelial cells following binding to surface components of host cells, which serve as receptors for the bacterium. Evidence is presented in this study that shows that transglutaminase 2 (TG2) plays a critical role in the adherence of P. gingivalis to host cells. Studies of confocal microscopy indicate colocalization of P. gingivalis with TG2 on the surface of HEp-2 epithelial cells, with clusters of TG2 seen at bacterial attachment sites. By silencing the expression of TG2 with siRNA in HEp-2 cells, P. gingivalis association was greatly diminished. The bacterium does not bind well to a mouse fibroblast cell line that produces low amounts of surface TG2, but binding can be restored by introduction of TG2 expressed on a plasmid. TG2 can form very tight complexes with fibronectin (FN), and the complementary binding sites of the two proteins are known. A synthetic peptide that mimics the main FN-binding sequence of TG2 blocks the formation of TG2-FN complexes and is highly effective in inhibiting adherence of P. gingivalis to host cells. These findings provide evidence of a role for cell-surface TG2 in bacterial attachment and subsequent internalization.

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“…These findings suggested that both proteolytic activation of PAR-2 by gingipains and the endocytosis of P. gingivalis are required for the up-regulation of IL-33 expression induced by P. gingivalis in oral epithelial cells. P. gingivalis enters gingival epithelial cells by endocytosis, which mediates binding of Rgp to the cells [22]. It must be noted that gingipains are required for maturation of P. gingivalis fimbriae [23], which is essential for internalization of the bacterium into epithelial cells [24].…”

Section: Role Of Par-2 In the Induction Of Il-33 By Gingipainsmentioning

confidence: 99%

Possible Roles of IL-33 in Periodontal Diseases: Porphyromonas gingivalis Induced IL-33 in Human Gingival Epithelial Cells

Tada

Shimauchi

Takada

et al. 2015

Interface Oral Health Science 2014

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In the oral mucosa, epithelial cells work not only as a physical barrier to pathogens, but also play a pivotal role in initiating immune responses to microbes. Interleukin (IL)-33, a member of the IL-1 family, is constitutively expressed in epithelial cells and amplifies Th2-type inflammatory immune responses. We found that IL-33 was detected in the inflamed gingival epithelium from chronic periodontitis patients, and periodontopathic Porphyromonas gingivalis strongly increased expressions of IL-33 mRNA and molecules in human gingival epithelial cells. In contrast, fimbriae, a lipopeptide and lipopolysaccharide derived from P. gingivalis were not active in this respect. Protease inhibitors specific for gingipains efficiently inhibited the induction of IL-33 mRNA by stimulation with P. gingivalis. Furthermore, P. gingivalis KDP136, a gingipains-null mutant, did not increase IL-33 mRNA expression. We also demonstrated that P. gingivalis upregulated IL-33 mRNA expression through protease-activated receptor-2, phospholipase C, mitogen-activated protein kinase p38 and NF-κB. IL-33 is suggested to negatively regulate antimicrobial peptide LL-37, resulting in attenuation of innate immune responses of gingival epithelial cells in chronic periodontitis. Possible roles of IL-33 in inflammation in the oral mucosa are discussed.

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Clathrin-dependent entry of a gingipain adhesin peptide andPorphyromonas gingivalisinto host cells

Cited by 28 publications

References 60 publications

Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion

Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion

Transglutaminase 2 is essential for adherence of Porphyromonas gingivalis to host cells

Possible Roles of IL-33 in Periodontal Diseases: Porphyromonas gingivalis Induced IL-33 in Human Gingival Epithelial Cells

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