Research Progress of Gingipain of Porphyromonas Gingivalis

doi:10.13701/j.cnki.kqyxyj.2022.03.003

Abstract

Abstract: Periodontitis is a chronic inflammatory disease of tooth-supporting tissues. It could give a rise to a progressive loss of attachment by destructing the connective tissue and alveolar bone, and may eventually lead to tooth loss. Gram-negative anaerobic bacterium Porphyromonas gingivalis (P. gingivalis) is an important pathogen of chronic periodontitis, which expresses several virulence factors, including lipopolysaccharide, fimbriae, hemagglutinins, and cysteine proteinases. Among them, gingipains (belonging to cysteine proteinases) account for most (85%) of the general proteolytic activity caused by P. gingivalis, and have been considered as the essential virulence factor. This review discusses the gingipains's classification, secretion, pathogenic effects, and inhibitors.

Key words: Porphyromonas gingivalis, gingipains, periodontitis, proteolysis, immune evasion

WANG Dan, MENG Weiyan. Research Progress of Gingipain of Porphyromonas Gingivalis[J]. Journal of Oral Science Research, 2022, 38(3): 216-219.

References

[1] Veillard F, Sztukowska M, Nowakowska Z, et al. Proteolytic processing and activation of gingipain zymogens secreted by T9SS of Porphyromonas gingivalis [J]. Biochimie, 2019, 166: 161-172.
[2] O'Brien-Simpson NM, Paolini RA, Hoffmann B, et al. Role of RgpA, RgpB, and Kgp proteinases in virulence of Porphyromonas gingivalis W50 in a murine lesion model [J]. Infect Immun, 2001, 69(12): 7527-7534.
[3] Naito M, Tominaga T, Shoji M, et al. PGN_0297 is an essential component of the type Ⅸ secretion system (T9SS) in Porphyromonas gingivalis: Tn-seq analysis for exhaustive identification of T9SS-related genes [J]. Microbiol Immunol, 2019, 63(1): 11-20.
[4] Lasica AM, Ksiazek M, Madej M, et al. The type Ⅸ secretion system (T9SS): Highlights and recent insights into its structure and function [J]. Front Cell Infect Microbiol, 2017, 7: 215.
[5] Benedyk M, Marczyk A, Chruscicka B. Type Ⅸ secretion system is pivotal for expression of gingipain-associated virulence of Porphyromonas gingivalis [J]. Mol Oral Microbiol, 2019, 34(6): 237-244.
[6] Taguchi Y, Sato K, Yukitake H, et al. Involvement of an Skp-like protein, PGN_0300, in the type Ⅸ secretion system of Porphyromonas gingivalis [J]. Infect Immun, 2016, 84(1): 230-240.
[7] Ono S, Nakayama M, Tachibana M, et al. Construction and characterization of a PGN_0297 mutant of Porphyromonas gingivalis: evidence of the contribution of PGN_0297 to gingipain activity [J]. Acta Med Okayama, 2019, 73(4): 315-323.
[8] Shen D, Perpich JD, Stocke KS, et al. Role of the RprY response regulator in P. gingivalis community development and virulence [J]. Mol Oral Microbiol, 2020, 35(6):231-239.
[9] Qiu Q, Zhang F, Wu J, et al. Gingipains disrupt F-actin and cause osteoblast apoptosis via integrin beta1 [J]. J Periodontal Res, 2018, 53(5): 762-776.
[10] Takeuchi H, Sasaki N, Yamaga S, et al. Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of junctional adhesion molecule 1 [J]. PLoS Pathog, 2019, 15(11): e1008124.
[11] Zhang F, Qiu Q, Song X, et al. Signal-regulated protein kinases/protein kinase B-p53-BH3-interacting domain death agonist pathway regulates gingipain-induced apoptosis in osteoblasts [J]. J Periodontol, 2017, 88(11): e200-e210.
[12] Mo W, Luo H, Wu J, et al. Gingipains promote RANKL-induced osteoclastogenesis through the enhancement of integrin β3 in RAW264.7 cells [J]. J Mol Histol, 2020, 51(2): 147-159.
[13] Gürsoy UK, Fteita D, Bikker FJ, et al. Elevated baseline salivary protease activity may predict the steadiness of gingival inflammation during periodontal healing: A 12-week follow-up study on adults [J]. Pathogens, 2020, 9(9):751.
[14] Tada H, Matsuyama T, Nishioka T, et al. Porphyromonas gingivalis gingipain-dependently enhances IL-33 production in human gingival epithelial cells [J]. PLoS One, 2016, 11(4): e0152794.
[15] Tada H, Nishioka T, Takase A, et al. Porphyromonas gingivalis induces the production of interleukin-31 by human mast cells, resulting in dysfunction of the gingival epithelial barrier [J]. Cell Microbiol, 2019, 21(3): e12972.
[16] Jun HK, An SJ, Kim HY, et al. Inflammatory response of uric acid produced by Porphyromonas gingivalis gingipains [J]. Mol Oral Microbiol, 2020, 35(5): 222-230.
[17] Jun HK, Jung YJ, Choi BK. Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia induce cell death and release of endogenous danger signals [J]. Arch Oral Biol, 2017, 73: 72-78.
[18] Wilensky A, Tzach-Nahman R, Potempa J, et al. Porphyromonas gingivalis gingipains selectively reduce CD14 expression, leading to macrophage hyporesponsiveness to bacterial infection [J]. J Innate Immun, 2015, 7(2): 127-135.
[19] Castro SA, Collighan R, Lambert PA, et al. Porphyromonas gingivalis gingipains cause defective macrophage migration towards apoptotic cells and inhibit phagocytosis of primary apoptotic neutrophils [J]. Cell Death Dis, 2017, 8(3): e2644.
[20] Byon MJ, Kim SY, Kim JS, et al. Association of periodontitis with atherosclerotic cardiovascular diseases: A nationwide population-based retrospective matched cohort study [J]. Int J Environ Res Public Health, 2020, 17(19):7261.
[21] Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors [J]. Sci Adv, 2019, 5(1): eaau3333.
[22] Seyama M, Yoshida K, Yoshida K, et al. Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver [J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(6): 165731.
[23] Lonn J, Ljunggren S, Klarstrom-Engstrom K, et al. Lipoprotein modifications by gingipains of Porphyromonas gingivalis [J]. J Periodontal Res, 2018, 53(3): 403-413.
[24] Hajishengallis G. Oral bacteria and leaky endothelial junctions in remote extraoral sites [J]. FEBS J, 2021, 288(5):1475-1478.
[25] Liu Y, Wu Z, Nakanishi Y, et al. Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice [J]. Sci Rep, 2018, 8(1):10304.
[26] Nonaka S, Nakanishi H. Secreted gingipains from Porphyromonas gingivalis induce microglia migration through endosomal signaling by protease-activated receptor 2 [J]. Neurochem Int, 2020, 140: 104840.
[27] Haditsch U, Roth T, Rodriguez L, et al. Alzheimer's disease-like neurodegeneration in porphyromonas gingivalis Infected neurons with persistent expression of active gingipains [J]. J Alzheimers Dis, 2020, 75(4): 1361-1376.
[28] Hosn KN, Jefferson M, Leding C, et al. Inhibitors of bacterial protease enzymes for periodontal therapy [J]. Clin Exp Dent Res, 2015, 1(1): 18-25.
[29] Kariu T, Ikeda T, Nakashima K, et al. A natural anti-periodontitis agent, epimedokoreanin B, inhibits virulence activities of gingipains from Porphyromonas gingivalis[J]. Biosci Biotechnol Biochem, 2019, 83(7): 1382-1384.
[30] Eltigani SA, Eltayeb MM, Bito T, et al. Argeloside I inhibits the pathogenicity of Porphyromonas gingivalis TDC60 [J]. J Biosci Bioeng, 2020, 130(6): 644-649.