Functional Differences among FimA Variants of Porphyromonas gingivalis and Their Effects on Adhesion to and Invasion of Human Epithelial Cells

Abstract

Fimbriae of Porphyromonas gingivalis, a periodontopathogen, play an important role in its adhesion to and invasion of host cells. The fimA genes encoding fimbrillin (FimA), a subunit protein of fimbriae, have been classified into five types, types I to V, based on nucleotide sequences. We previously reported that P. gingivalis with type II fimA was strongly associated with adult periodontitis. In the present study, we compared the abilities of recombinant FimA (rFimA) types I to V to adhere to and invade human gingival fibroblasts (HGF) and a human epithelial cell line (HEp-2 cells) by using rFimA-conjugated microspheres (rFimA-MS). There were no significant differences in the abilities of the rFimA-MS to adhere to HGF; however, the adhesion of type II rFimA-MS to HEp-2 cells was significantly greater than those of other types of rFimA-MS. We also observed that type II rFimA-MS invaded epithelial cells and accumulated around the nuclei. These adhesion and invasion characteristics were eliminated by the addition of antibodies to type II rFimA and ␣5␤1-integrin. In contrast, Arg-Gly-Asp-Ser peptide and a synthetic peptide of proline-rich protein C had negligible inhibitory effects. Furthermore, P. gingivalis strain HW24D1 with type II fimA adhered to cells and invaded them more than strains with other fimA genotypes. These results suggest that type II FimA can bind to epithelial cells most efficiently through specific host receptors.

Pathogenic Factors of P. gingivalis and the Host Defense Mechanisms

“…3B). This observation is in good accord with previous data, which showed accumulation of internalized recombinant FimA-microspheres around the epithelial cell nuclei (Nakagawa et al, 2002a). www.intechopen.com concentration in gingival epithelial cells, suggesting an involvement of a Ca 2+ -dependent signaling pathway (Izutsu et al, 1996).…”

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

“…Based on karyotyping, the HEp-2 cell line has been reclassified as HeLa (44). Both cell lines have been used extensively to study host-bacterial interactions, including those with P. gingivalis (5,9,45,46), and, in the present study, we used HEp-2 cells to maintain consistency with previous work (7,17). The mouse NIH/3T3 fibroblast cell line was purchased from the American Type Culture Collection (ATCC) and cultivated in DMEM supplemented with 10% FCS.…”

“…gingivalis binds to several human cell types and is internalized upon attachment; adherence and entry are mediated by bacterial surface structures such as fimbriae (5,6) and gingipain cysteine proteinases (7)(8)(9). A number of surface components of eukaryotic cells have been suggested to serve as receptors.…”

“…A number of surface components of eukaryotic cells have been suggested to serve as receptors. 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).…”

Is Porphyromonas gingivalis Cell Invasion Required for Atherogenesis? Pharmacotherapeutic Implications

“…Porphyromonas gingivalis, which has been strongly associated with adult periodontitis, is a Gram-negative, nonmotile, obligate anaerobe that can invade and infect epithelium, endothelium, and vascular smooth muscle cells (6 -9) and appears to alter endothelial function (10). The capacity for invasion and the subsequent inflammatory responses is in part mediated by fimbriae (11)(12)(13), and the virulence of P. gingivalis may vary among individual strains depending on which one of the five major types of FimA gene they possess (14).…”