Systematic Review: Porphyromonas gingivalis Gingipain Plays a Vital Role in Organ Dysfunction in Systemic Diseases
DOI:
https://doi.org/10.18196/imunity.v1i1.2Keywords:
Gingipain, Organ dysfunction, P. gingivalis, systemic diseasesAbstract
Current literature suggests a vital role for Porphyromonas gingivalis (P. gingivalis) gingipain in organ dysfunction in systemic disorders. Apart from triggering organ damage in periodontal tissue, gingipain is thought to be related to the pathogenicity of P. gingivalis in systemic diseases because it is related to its proteolytic activity. Thus, this systematic review aimed to comprehensively study the role of gingipain P and gingivalis in triggering organ dysfunction in systemic disorders. An electronic search was conducted in two databases (Pubmed and Science Direct) to identify studies published from January 2014 to January 2024. Results After the screening process, 18 in-vitro, in vivo, and clinical studies met the inclusion criteria and were included for further assessment. All studies have reported that P. gingivalis gingipain can significantly trigger cell, tissue, and organ damage. This process is activated through various inflammatory and oxidative stress mediators and pathways. The involvement of P. gingivalis OMVs and the proteolytic activity of gingipain in tight junctions was associated with tissue and organ damage outside the periodontal tissue. Briefly, based on the results of this study, P. gingivalis gingipain plays a role in provoking organ dysfunction in systemic disorders.
References
Kemenkes RI. Laporan Nasional: RISKESDAS 2018. Jakarta; 2018.
Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global Prevalence of Periodontal Disease and Lack of Its Surveillance. Sci World J. 2020;2020.
Chopra A, Bhat SG, Sivaraman K. Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update. J Oral Microbiol [Internet]. 2020;12(1). Available from: https://doi.org/10.1080/20002297.2020.1801090
Tribble GD, Kerr JE, Wang B. Genetic diversity in the oral pathogen Porphyromonas gingivalis: molecular mechanisms and biological consequences. Futur Microbiol. 2013;8(5):607–20.
Khurshid Z, Mali M, Naseem M, Najeeb S, Zafar M. Human Gingival Crevicular Fluids (GCF) Proteomics: An Overview. Dent J [Internet]. 2017;5(1):12. Available from: http://www.mdpi.com/2304-6767/5/1/12
Charoensaensuk V, Chen Y-C, Lin Y-H, Ou K-L, Yang L-Y, Lu D-Y. Porphyromonas gingivalis Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells. cells. 2021;10(3033):1–21.
Wang T, Ishikawa T, Sasaki M, Chiba T. Oral and Gut Microbial Dysbiosis and Non-alcoholic Fatty Liver Disease: The Central Role of Porphyromonas gingivalis. Front Med. 2022;9(March):1–16.
How KY, Song KP, Chan KG, Caldwell CC. Porphyromonas gingivalis : An Overview of Periodontopathic Pathogen below the Gum Line. Front Microbiol. 2016;7(February):1–14.
Bengtsson T, Khalaf A, Khalaf H. Secreted gingipains from Porphyromonas gingivalis colonies exert potent immunomodulatory effects on human gingival fibroblasts. Microbiol Res [Internet]. 2015;178:18–26. Available from: http://dx.doi.org/10.1016/j.micres.2015.05.008
Takii R, Kadowaki T, Baba A, Tsukuba T, Yamamoto K. A functional virulence complex composed of gingipains, adhesins, and lipopolysaccharide shows high affinity to host cells and matrix proteins and escapes recognition by host immune systems. Infect Immun. 2005;73(2):883–93.
Li N, Collyer CA. Gingipains from Porphyromonas gingivalis — complex domain structures confer diverse functions . Eur J Microbiol Immunol. 2011;1(1):41–58.
Nonaka S, Kadowaki T, Nakanishi H. Secreted gingipains from Porphyromonas gingivalis increase permeability in human cerebral microvascular endothelial cells through intracellular degradation of tight junction proteins. Neurochem Int [Internet]. 2022;154(December 2021):105282. Available from: https://doi.org/10.1016/j.neuint.2022.105282
de Jongh CA, Bikker FJ, de Vries TJ, Werner A, Gibbs S, Krom BP. Porphyromonas gingivalis interaction with Candida albicans allows for aerobic escape, virulence and adherence. Biofilm [Internet]. 2024;7(August 2023):100172. Available from: https://doi.org/10.1016/j.bioflm.2023.100172
Du F, Zhu Z, Lai Z, Li K, Chen J, Zhang E, et al. Imbalance of helper T cell subtypes and adipokine secretion in perivascular adipose tissue as a trigger of atherosclerosis in chronic Porphyromonas gingivalis W83 infection. Microbes Infect [Internet]. 2023;25(8):105181. Available from: https://doi.org/10.1016/j.micinf.2023.105181
He Y, Shiotsu N, Uchida-Fukuhara Y, Guo J, Weng Y, Ikegame M, et al. Outer membrane vesicles derived from Porphyromonas gingivalis induced cell death with disruption of tight junctions in human lung epithelial cells. Arch Oral Biol [Internet]. 2020;118(May):104841. Available from: https://doi.org/10.1016/j.archoralbio.2020.104841
Wang YX, Kang XN, Cao Y, Zheng DX, Lu YM, Pang CF, et al. Porphyromonas gingivalis induces depression via downregulating p75NTR-mediated BDNF maturation in astrocytes. Brain Behav Immun [Internet]. 2019;81(March):523–34. Available from: https://doi.org/10.1016/j.bbi.2019.07.012
Aly LA, El-Menoufy H, Elsharkawy RT, Zaghloul MZ, Sabry D. Maternal chronic oral infection with periodontitis and pericoronitis as a possible risk factor for preeclampsia in Egyptian pregnant women (microbiological and serological study). Futur Dent J [Internet]. 2015;1(1):23–32. Available from: http://dx.doi.org/10.1016/j.fdj.2015.11.002
Ma X, Shin YJ, Yoo JW, Park HS, Kim DH. Extracellular vesicles derived from Porphyromonas gingivalis induce trigeminal nerve-mediated cognitive impairment. J Adv Res [Internet]. 2023;54:293–303. Available from: https://doi.org/10.1016/j.jare.2023.02.006
Ma X, Yoo JW, Shin YJ, Park HS, Son YH, Kim DH. Alleviation of Porphyromonas gingivalis or Its Extracellular Vesicles Provoked Periodontitis and Cognitive Impairment by Lactobacillus pentosus NK357 and Bifidobacterium bifidum NK391. Nutrients. 2023;15(5).
Shiheido-Watanabe Y, Maejima Y, Nakagama S, Fan Q, Tamura N, Sasano T. Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion. Int J Oral Sci. 2023;15(1):1–15.
Song LT, Tada H, Nishioka T, Nemoto E, Imamura T, Potempa J, et al. Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells. J Innate Immun. 2022;14(4):306–19.
Tada H, Nishioka T, Takase A, Numazaki K, Bando K, Matsushita K. Porphyromonas gingivalis induces the production of interleukin-31 by human mast cells, resulting in dysfunction of the gingival epithelial barrier. Cell Microbiol. 2019;21(3):1–13.
Mu W, Jia Y, Chen X, Li H, Wang Z, Cheng B. Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway. Front Cell Infect Microbiol. 2020;10(December):1–13.
Istomin N, Härma MA, Akhi R, Nissinen AE, Savolainen MJ, Adeshara K, et al. Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery. Apmis. 2022;130(11):637–46.
Shiheido Y, Maejima Y, Suzuki J ichi, Aoyama N, Kaneko M, Watanabe R, et al. Porphyromonas gingivalis, a periodontal pathogen, enhances myocardial vulnerability, thereby promoting post-infarct cardiac rupture. J Mol Cell Cardiol [Internet]. 2016;99:123–37. Available from: http://dx.doi.org/10.1016/j.yjmcc.2016.03.017
Heo SC, Kim YS, Kim YN, Kim JH, Kim HJ. Virulence factors released from Porphyromonas gingivalis induce electrophysiological dysfunction in human pluripotent stem cell-derived cardiomyocytes. J Dent Sci [Internet]. 2022;17(4):1559–65. Available from: https://doi.org/10.1016/j.jds.2022.04.013
Jun HK, Jung YJ, Choi BK. Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia induce cell death and release of endogenous danger signals. Arch Oral Biol [Internet]. 2017;73:72–8. Available from: http://dx.doi.org/10.1016/j.archoralbio.2016.09.010
Lysek R, Jankowski P, Polak M, Szafraniec K, Micek A, Wolfshaut-Wolak R, et al. Association between central and peripheral blood pressure and periodontal disease in patients with a history of myocardial infarction. Pol Arch Med Wewn. 2016;126(1–2):41–7.
Ilievski V, Zuchowska PK, Green SJ, Toth PT, Ragozzino ME, Le K, et al. Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice. PLoS One. 2018;13(10):1–24.
Seymour T, Zhang J. Porphyromonas Gingivalis in the Pathogenesis of Alzheimer’s Disease and Its Therapeutic Target . J Explor Res Pharmacol [Internet]. 2022;7(1):45–53. Available from: https://www.doi.org/10.14218/JERP.2021.00030
Ding Y, Ren J, Yu H, Yu W, Zhou Y. Porphyromonas gingivalis, a periodontitis causing bacterium, induces memory impairment and age-dependent neuroinflammation in mice. Immun Ageing. 2018;15(1):1–8.
Mahendra J, Mahendra L, Sharma V, Alamoudi A, Bahammam HA, Mugri MH, et al. Red-Complex Bacterial Levels in Pregnant Women With Preeclampsia and Chronic Periodontitis. Int Dent J [Internet]. 2022;0:1–8. Available from: https://doi.org/10.1016/j.identj.2022.10.003
Kosyreva AM, Simonova EY. Histophysiology of the immune system of wistar rats at delayed terms after ovariectomy. Bull Exp Biol Med. 2013;155(5):697–700.
Bhattacharya R, Xu F, Dong G, Li S, Tian C, Ponugoti B, et al. Effect of bacteria on the wound healing behavior of oral epithelial cells. PLoS One. 2014;9(2):1–10.
Staines KA, MacRae VE, Farquharson C. The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling. J Endocrinol. 2012;214(3):241–55.
Chen WA, Dou Y, Fletcher HM, Boskovic DS. Local and Systemic Effects of Porphyromonas gingivalis Infection. Microorganisms. 2023;11(2):1–27.
Lin J, Huang D, Xu H, Zhan F, Tan XL. Macrophages: A communication network linking Porphyromonas gingivalis infection and associated systemic diseases. Front Immunol. 2022;13(July):1–11.
Sansores-España LD, Melgar-Rodríguez S, Olivares-Sagredo K, Cafferata EA, Martínez-Aguilar VM, Vernal R, et al. Oral-Gut-Brain Axis in Experimental Models of Periodontitis: Associating Gut Dysbiosis With Neurodegenerative Diseases. Front Aging. 2021;2(December):1–21.
Nunes JM, Fillis T, Page MJ, Venter C, Lancry O, Kell DB, et al. Gingipain R1 and Lipopolysaccharide From Porphyromonas gingivalis Have Major Effects on Blood Clot Morphology and Mechanics. Front Immunol. 2020;11(July):1–15.
Olsen I, Lambris JD, Hajishengallis G. Porphyromonas gingivalis disturbs host–commensal homeostasis by changing complement function. J Oral Microbiol [Internet]. 2017;9(1). Available from: https://doi.org/10.1080/20002297.2017.1340085
Meenakshi S, Varghese SS. Periodontal vaccines: A systematic review. Brazilian Dent Sci. 2020;23(1).
Barth K, Genco CA. Microbial degradation of cellular kinases impairs innate immune signaling and paracrine TNFα responses. Sci Rep [Internet]. 2016;6(May):1–18. Available from: http://dx.doi.org/10.1038/srep34656
Ruan Q, Guan P, Qi W, Li J, Xi M, Xiao L, et al. Porphyromonas gingivalis regulates atherosclerosis through an immune pathway. Front Immunol. 2023;14(March):1–21.
Kusumawardani, B., Arina, Y. M., & Purwandhono, A. . Perkembangan Plasenta dan Pertumbuhan Janin pada Tikus Hamil yang Diinfeksi Porphyromonas Gingivalis Placental Development and Fetal Growth in Porphyromonas Gingivalis-Infected Pregnant Rats. Insisiva Dental Journal: Majalah Kedokteran Gigi Insisiva 2014; 3(1), 22-29.
