Review- The periodontal pathogen Treponema denticola: an atherosclerosis risk factor

Authors

DOI:

https://doi.org/10.33448/rsd-v10i1.11637

Keywords:

Treponema denticola; Periodontal Diseases; Atherosclerosis.

Abstract

Objective: Treponema denticola “T. denticola” is a pathogen associated with periodontal diseases that exhibits capacity for adherence, invasion, and colonization of host tissues, which allows alternating its location and damage in different sites of human body. This review aimed to discuss different studies that detected T. denticola in atherosclerotic plaques, demonstrating the importance of periodontal disease on the systemic health and the necessity of exploring the outcome of this colonization apart from the oral cavity. Methodology: Fifty-five studies were identified and gathered in this review according to the following topics: Periodontal disease, atherosclerosis and T. denticola. In vitro and in vivo studies published between 2002 and 2020 were searched on PubMed, raising relevant insights about the role of T. denticola and its association with the systemic disease, atherosclerosis, focusing on the bacterial tissue invasion and development of atherosclerosis. Results: After bibliographic review, it was possible to identify studies demonstrating the presence of T. denticola and other oral pathogens in cardiac or vascular tissues and in blood serum, as well, there is research in which other evidence of a relationship with atherosclerosis is shown. Conclusion: The invasion of periodontal pathogens and its toxins associated to the host’s immune and inflammatory response may contribute to the development of atherosclerosis.

Author Biography

Patrícia Michelle Nagai de Lima, São Paulo State University

São Paulo State University (UNESP). Institute of Science and Technology. Department of Biosciences and Oral Diagnosis. São José dos Campos, SP, Brazil. 12245-000. 

References

Abiko, Y., Nagano, K., Yoshida, Y., & Yoshimura, F. (2014). Characterization of Treponema denticola mutants defective in the major antigenic proteins, Msp and TmpC. Plos One, 9(11), e113565. 10.1371/journal.pone.0113565

Aquino, A. R. L., Lima, K. C., Paiva, M. S., Rôças, I. N., & Siqueira, J. F. (2011). Molecular survey of atheromatous plaques for the presence of DNA from periodontal bacterial pathogens, archaea and fungi. Journal of periodontal research, 46(3), 303–309. 10.1111/j.1600-0765.2010.01343.x

Bale, B. F., Doneen, A. L., & Vigerust, D. J. (2017). High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis. Postgraduate Medical Journal, 93(1098), 215–220. 10.1136/postgradmedj-2016-134279

Bui, F. Q., Almeida-da-Silva, C. L. C., Huynh, B., Trinh, A., Liu, J., Woodward, J., & Ojcius, D. M. (2019). Association between periodontal pathogens and systemic disease. Biomedical journal, 42(1), 27–35. 10.1016/j.bj.2018.12.001

Chu, L., Wu, Y., Xu, X., Phillips, L., & Kolodrubetz, D. (2020). Glutathione catabolism by Treponema denticola impacts its pathogenic potential. Anaerobe, 62, 102170. 10.1016/j.anaerobe.2020.102170

Chukkapalli, S. S., Rivera, M. F., Velsko, I. M., Lee, J.-Y., Chen, H., Zheng, D., & Kesavalu, L. (2014). Invasion of oral and aortic tissues by oral spirochete Treponema denticola in ApoE(-/-) mice causally links periodontal disease and atherosclerosis. Infection and Immunity, 82(5), 1959–1967. 10.1128/IAI.01511-14

Dahlen, G., & Preus, H. R. (2017). Low antibiotic resistance among anaerobic Gram-negative bacteria in periodontitis 5 years following metronidazole therapy. Anaerobe, 43, 94–98. 10.1016/j.anaerobe.2016.12.009

Dashper, S. G., Seers, C. A., Tan, K. H., & Reynolds, E. C. (2011). Virulence factors of the oral spirochete Treponema denticola. Journal of Dental Research, 90(6), 691–703. 10.1177/0022034510385242

Deinzer, R., Granrath, N., Spahl, M., Linz, S., Waschul, B., & Herforth, A. (2005). Stress, oral health behaviour and clinical outcome. British journal of health psychology, 10(Pt 2), 269–283. 10.1348/135910705X26858

Dentino, A., Lee, S., Mailhot, J., & Hefti, A. F. (2013). Principles of periodontology. Periodontology 2000, 61(1), 16–53. 10.1111/j.1600-0757.2011.00397.x

Fenno, J. C. (2012). Treponema denticola interactions with host proteins. Journal of oral microbiology, 4. doi:10.3402/jom.v4i0.9929

Gangula, P., Ravella, K., Chukkapalli, S., Rivera, M., Srinivasan, S., Hale, A., & Kesavalu, L. (2015). Polybacterial Periodontal Pathogens Alter Vascular and

Gut BH4/nNOS/NRF2-Phase II Enzyme Expression. Plos One, 10(6), e0129885. 10.1371/journal.pone.0129885

Genco, R. J., & Borgnakke, W. S. (2013). Risk factors for periodontal disease. Periodontology 2000, 62(1), 59–94. 10.1111/j.1600-0757.2012.00457.x

Gisterå, A., & Hansson, G. K. (2017). The immunology of atherosclerosis. Nature Reviews. Nephrology, 13(6), 368–380. 10.1038/nrneph.2017.51

Gu, Z., Singh, S., Niyogi, R. G., Lamont, G. J., Wang, H., Lamont, R. J., & Scott, D. A. (2019). Marijuana-Derived Cannabinoids Trigger a CB2/PI3K Axis of Suppression of the Innate Response to Oral Pathogens. Frontiers in immunology, 10, 2288. 10.3389/fimmu.2019.02288

Heidari, Z., Moudi, B., & Mahmoudzadeh-Sagheb, H. (2019). Immunomodulatory factors gene polymorphisms in chronic periodontitis: an overview. BMC oral health, 19(1), 29. 10.1186/s12903-019-0715-7

Herrington, D. M., Mao, C., Parker, S. J., Fu, Z., Yu, G., Chen, L., & Van Eyk, J. E. (2018). Proteomic architecture of human coronary and aortic atherosclerosis. Circulation, 137(25), 2741–2756. 10.1161/CIRCULATIONAHA.118.034365

Herrington, W., Lacey, B., Sherliker, P., Armitage, J., & Lewington, S. (2016). Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circulation Research, 118(4), 535–546. 10.1161/CIRCRESAHA.115.307611

Inagaki, S., Kimizuka, R., Kokubu, E., Saito, A., & Ishihara, K. (2016). Treponema denticola invasion into human gingival epithelial cells. Microbial Pathogenesis, 94, 104–111. 10.1016/j.micpath.2016.01.010

Ishihara, K. (2010). Virulence factors of Treponema denticola. Periodontology 2000, 54(1), 117–135. 10.1111/j.1600-0757.2009.00345.x

Jun, H.-K., Jung, Y.-J., & Choi, B.-K. (2017). Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia induce cell death and release of endogenous danger signals. Archives of Oral Biology, 73, 72–78. 10.1016/j.archoralbio.2016.09.010

Kaushik, S. N., Scoffield, J., Andukuri, A., Alexander, G. C., Walker, T., Kim, S., & Cheon, K. (2015). Evaluation of ciprofloxacin and metronidazole encapsulated biomimetic nanomatrix gel on Enterococcus faecalis and Treponema denticola. Biomaterials research, 19, 9. doi:10.1186/s40824-015-0032-4

Kikuchi, Y., & Ishihara, K. (2021). Characterization of the Treponema denticola Virulence Factor Dentilisin. Methods in Molecular Biology, 2210, 173–184. 10.1007/978-1-0716-0939-2_17

Kikuchi, Y., Kimizuka, R., Kato, T., Okuda, K., Kokubu, E., & Ishihara, K. (2018). Treponema denticola Induces Epithelial Barrier Dysfunction in Polarized Epithelial Cells. The Bulletin of Tokyo Dental College, 59(4), 265–275. 10.2209/tdcpublication.2017-0052

Kobiyama, K., & Ley, K. (2018). Atherosclerosis. Circulation Research, 123(10), 1118–1120. 10.1161/CIRCRESAHA.118.313816

Kokubu, E., Inoue, T., & Ishihara, K. (2018). Response of epithelial cells infected by Treponema denticola. Oral Diseases, 24(1-2), 14–18. 10.1111/odi.12794

Li, B., Xia, Y., & Hu, B. (2020). Infection and atherosclerosis: TLR-dependent pathways. Cellular and Molecular Life Sciences, 77(14), 2751–2769. 10.1007/s00018-020-03453-7

Libby, P., Buring, J. E., Badimon, L., Hansson, G. K., Deanfield, J., Bittencourt, M. S., & Lewis, E. F. (2019). Atherosclerosis. Nature reviews. Disease primers, 5(1), 56. 10.1038/s41572-019-0106-z

Loyola-Rodriguez, J. P., Garcia-Cortes, J. O., Martinez-Martinez, R. E., Patiño-Marin, N., Martinez-Castañon, G. A., Zavala-Alonso, N. V., & Amano, A. (2014). Molecular identification and antibiotic resistant bacteria isolated from primary dentition infections. Australian dental journal, 59(4), 497–503. 10.1111/adj.12213

Mahendra, J., Mahendra, L., Kurian, V. M., Jaishankar, K., & Mythilli, R. (2009). Prevalence of periodontal pathogens in coronary atherosclerotic plaque of patients undergoing coronary artery bypass graft surgery. Journal of maxillofacial and oral surgery, 8(2), 108–113. 10.1007/s12663-009-0028-5

Maixner, F., Thomma, A., Cipollini, G., Widder, S., Rattei, T., & Zink, A. (2014). Metagenomic analysis reveals presence of Treponema denticola in a tissue biopsy of the Iceman. Plos One, 9(6), e99994. 10.1371/journal.pone.0099994

Marttila, E., Järvensivu, A., Sorsa, T., Grenier, D., Richardson, M., Kari, K., & Rautemaa, R. (2014). Intracellular localization of Treponema denticola chymotrypsin-like proteinase in chronic periodontitis. Journal of oral microbiology, 6.:10.3402/jom.v6.24349

Miao, D., Godovikova, V., Qian, X., Seshadrinathan, S., Kapila, Y. L., & Fenno, J. C. (2014). Treponema denticola upregulates MMP-2 activation in periodontal ligament cells: interplay between epigenetics and periodontal infection. Archives of Oral Biology, 59(10), 1056–1064. 10.1016/j.archoralbio.2014.06.003

Middeke, M. (2019). [development, diagnosis and prevention of arteriosclerosis]. Deutsche Medizinische Wochenschrift, 144(5), 293. 10.1055/a-0796-6875

Miller, D. P., McDowell, J. V., Bell, J. K., Goetting-Minesky, M. P., Fenno, J. C., & Marconi, R. T. (2014). Analysis of the complement sensitivity of oral treponemes and the potential influence of FH binding, FH cleavage and dentilisin activity on the pathogenesis of periodontal disease. Molecular oral microbiology, 29(5), 194–207. 10.1111/omi.12054

Misaki, T., Fukunaga, A., Shimizu, Y., Ishikawa, A., & Nakano, K. (2019). Possible link between dental diseases and arteriosclerosis in patients on hemodialysis. Plos One, 14(12), e0225038. 10.1371/journal.pone.0225038

Mo, S., You, M., Su, Y. C. F., Lacap-Bugler, D. C., Huo, Y., Smith, G. J. D., & Watt, R. M. (2013). Multilocus sequence analysis of Treponema denticola strains of diverse origin. BMC Microbiology, 13, 24. 10.1186/1471-2180-13-24

Mohanty, R., Asopa, S. J., Joseph, M. D., Singh, B., Rajguru, J. P., Saidath, K., & Sharma, U. (2019). Red complex: Polymicrobial conglomerate in oral flora: A review. Journal of family medicine and primary care, 8(11), 3480–3486. 10.4103/jfmpc.jfmpc_759_19

Nagano, K., Hasegawa, Y., Yoshida, Y., & Yoshimura, F. (2017). Comparative analysis of motility and other properties of Treponema denticola strains. Microbial Pathogenesis, 102, 82–88. 10.1016/j.micpath.2016.11.021

Nagao, Y., & Tanigawa, T. (2019). Red complex periodontal pathogens are risk factors for liver cirrhosis. Biomedical reports, 11(5), 199–206. 10.3892/br.2019.1245

Ng, H. M., Slakeski, N., Butler, C. A., Veith, P. D., Chen, Y.-Y., Liu, S. W., & Reynolds, E. C. (2019). The Role of Treponema denticola Motility in Synergistic Biofilm Formation With Porphyromonas gingivalis. Frontiers in cellular and infection microbiology, 9, 432. doi:10.3389/fcimb.2019.00432

Paolicchi, A., Dominici, S., Pieri, L., Maellaro, E., & Pompella, A. (2002). Glutathione catabolism as a signaling mechanism. Biochemical Pharmacology, 64(5-6), 1027–1035. 10.1016/s0006-2952(02)01173-5

Pastore, A., Federici, G., Bertini, E., & Piemonte, F. (2003). Analysis of glutathione: implication in redox and detoxification. Clinica Chimica Acta, 333(1), 19–39. 10.1016/s0009-8981(03)00200-6

Radhakrishnan, P., Anbalagan, R., Barani, R., Mani, M., Seshadri, K. G., & Srikanth, P. (2019). Sequencing of Porphyromonas gingivalis from saliva in patients with periodontitis and type 2 diabetes mellitus. Indian Journal of Medical Microbiology, 37(1), 54–59. 10.4103/ijmm.IJMM_18_409

Raffaelli, L., Santangelo, R., Falchetti, P., Galluccio, F., Luciani, N., Anselmi, A., & D’Addona, A. (2010). Examination of periodontal pathogens in stenotic valve specimens and in whole blood samples in patients affected by aortic valve stenosis and chronic periodontitis. International Journal of Immunopathology and Pharmacology, 23(2), 561–566.

Rivera, M. F., Lee, J.-Y., Aneja, M., Goswami, V., Liu, L., Velsko, I. M., & Kesavalu, L. N. (2013). Polymicrobial infection with major periodontal pathogens induced periodontal disease and aortic atherosclerosis in hyperlipidemic ApoE(null) mice. Plos One, 8(2), e57178. 10.1371/journal.pone.0057178

Rizzacasa, B., Amati, F., Romeo, F., Novelli, G., & Mehta, J. L. (2019). Epigenetic modification in coronary atherosclerosis: JACC review topic of the week. Journal of the American College of Cardiology, 74(10), 1352–1365. 10.1016/j.jacc.2019.07.043

Ruby, J., Martin, M., Passineau, M. J., Godovikova, V., Fenno, J. C., & Wu, H. (2018). Activation of the Innate Immune System by Treponema denticola Periplasmic Flagella through Toll-Like Receptor 2. Infection and Immunity, 86(1). 10.1128/IAI.00573-17

Soto-Barreras, U., Olvera-Rubio, J. O., Loyola-Rodriguez, J. P., Reyes-Macias, J. F., Martinez-Martinez, R. E., Patiño-Marin, N., & Little, J. W. (2013). Peripheral arterial disease associated with caries and periodontal disease. Journal of periodontology, 84(4), 486–494. 10.1902/jop.2012.120051

Spacek, M., Zemanek, D., Hutyra, M., Sluka, M., & Taborsky, M. (2018). Vulnerable atherosclerotic plaque - a review of current concepts and advanced imaging. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, 162(1), 10–17. 10.5507/bp.2018.004

Torrungruang, K., Jitpakdeebordin, S., Charatkulangkun, O., & Gleebbua, Y. (2015). Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola / Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population. Plos One, 10(8), e0136646. 10.1371/journal.pone.0136646

Toyofuku, T., Inoue, Y., Kurihara, N., Kudo, T., Jibiki, M., Sugano, N., & Izumi, Y. (2011). Differential detection rate of periodontopathic bacteria in atherosclerosis. Surgery Today, 41(10), 1395–1400. 10.1007/s00595-010-4496-5

Velsko, I. M., Chukkapalli, S. S., Rivera-Kweh, M. F., Zheng, D., Aukhil, I., Lucas, A. R., & Kesavalu, L. (2015). Periodontal pathogens invade gingiva and aortic adventitia and elicit inflammasome activation in αvβ6 integrin-deficient mice. Infection and Immunity, 83(12), 4582–4593. 10.1128/IAI.01077-15

Verma, R. K., Rajapakse, S., Meka, A., Hamrick, C., Pola, S., Bhattacharyya, I., & Kesavalu, L. (2010). Porphyromonas gingivalis and Treponema denticola Mixed Microbial Infection in a Rat Model of Periodontal Disease. Interdisciplinary Perspectives on Infectious Diseases, 2010, 605125. 10.1155/2010/605125

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13/01/2021

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SANTOS, P. B. do R. E. dos .; LIMA, P. M. N. de .; PALMA, A. L. do R. .; HASNA, A. A. .; ROSSONI, R. D. .; JUNQUEIRA, J. C. .; OLIVEIRA, L. D. de . Review- The periodontal pathogen Treponema denticola: an atherosclerosis risk factor. Research, Society and Development, [S. l.], v. 10, n. 1, p. e25810111637, 2021. DOI: 10.33448/rsd-v10i1.11637. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/11637. Acesso em: 17 jan. 2021.

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Review Article