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

Abstract

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.

Oral Pathobiont Activates Anti-Apoptotic Pathway, Promoting both Immune Suppression and Oncogenic Cell Proliferation

“…P. gingivalis colonizes pre-malignant lesions of the esophagus 57 and OSCC 54 and has been called a keystone pathogen due to its outsized influence on the oral commensal microflora 55 . An invasive pathogen, P. gingivalis infects myeloid DCs 46 , endothelial cells 58 and epithelial cells 59 in periodontitis. P. gingivalis is able to survive in the host environment by evading autophagy in DCs 44 and is disseminated within migratory blood DCs 15 .…”

Transglutaminase 2 and Anti Transglutaminase 2 Autoantibodies in Celiac Disease and Beyond: TG2 Double-Edged Sword: Gut and Extraintestinal Involvement

“…It is considered as a biomarker of osteoarthritis and regulator of cartilage destruction and osteophyte and invadopodia formation [12][13][14]. Most recently TG2 was found to be essential for adherence of porphyromonas gingivalis (an environmental inducer of rheumatoid arthritis) to host cells [15]. In chronic kidney disease through the enhancement of matrix vesicleextracellular matrix interaction.…”

“…Just to enumerate some of them: elliptocytosis, EhlersDanlos syndrome type III, harlequin ichthyosis, ichthyosis bullosa, glucagon deficiency, pachyonychia congenital, α ketoglutarate dehydrogenase deficiency, phosphoglycerate dehydrogenase deficiency, alkaptinuria, Huntington's, recessive dystrophic epidermolysis bullosa, and cystic fibrosis [20]. 2,6,7,11,[13][14][15]17,19] Genetic Elliptocytosis, Ehlers-Danlos syndrome type III, harlequin ichthyosis, ichthyosis bullosa, glucagon deficiency, pachyonychia congenital, α ketoglutarate dehydrogenase deficiency, phosphoglycerate dehydrogenase deficiency, alkaptinuria, Huntington's, recessive dystrophic epidermolysis bullosa, cystic fibrosis [1,20] …”

Effects of the periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia on platelets

“…Further to this, P. gingivalis is known to interact with host cells through multiple pathways including targeting and manipulating integrin expression, such as integrin β1 (Yilmaz, Watanabe and Lamont, 2002; and β3 Boisvert, Lorand and Duncan, 2014). Within this chapter of work, it was investigated as to whether P. gingivalis could affect integrin β1 and β3 expression within the CHRF-288-11 cell line.…”

“…Additionally, an increase in clumping of platelets were seen when platelets were treated with P. gingivalis. Disruption in the expression of integrin β1 (Yilmaz, Watanabe and Lamont, 2002;, integrin β3 Boisvert, Lorand and Duncan, 2014) and in actin (Kinane et al, 2012) following P.…”