Role for fimbriae in Porphyromonas gulae invasion of oral epithelial cells

• Project/Area Number: 19K19266
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Okayama University
• Principal Investigator: Yoshida Sho 岡山大学, 医歯薬学総合研究科, 助教 (40801048)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 歯周病原菌 / 線毛 / fimA / 歯肉上皮細胞 / 付着侵入 / 人獣共通感染症 / 歯周病

Outline of Research at the Start

Porphyromonas gulaeは伴侶動物やその飼い主であるヒト口腔内の歯周病変部位から高頻度で検出される。そこで、P. gulae感染による歯周病発症メカニズムを解明することは、歯周病予防法の開拓につながるという着想に至った。本菌の菌体表層には線毛が存在し、線毛遺伝子はA/B/Cの3つの型に分類される。中でもP. gulae C型線毛保有株は高病原性を有するが、宿主への感染機構については未だ十分に明らかにされていない。本研究課題ではP. gulaeの歯肉上皮細胞への付着侵入機構を解析し、線毛の役割を明らかにし、歯周病発症メカニズムの一端を解明する。

Outline of Final Research Achievements

Porphyromonas gulae strains, classified into three genotypes (A, B, C) based on the diversity of fimA genes, were compared their human epithelial cells adhesion/invasion ability each other. We have shown the relation between invasion ability and fimA genotypes of P. gulae. And by using inhibitors suppress specific functions of the host cells, we have investigated the host cell adhesion/invasion routes of P. gulae. Furthermore we prepared fimA knockout P. gulae strain to evaluate pathogenesis of the fimbriae. The mutant strain based on P. gulae D049 has type C fimA gene was constructed by insertion erythromycin cassette into the fimA gene. The mutant strain will be used to investigate details of fimbriae pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

動物由来歯周病原菌 Porphyromonas gulae は伴侶動物を飼育する歯周病患者の病変部プラークから高頻度で検出され、歯周病は動物由来の P. gulae 感染による人獣共通感染症である可能性が考えられ始めている。本研究により P. gulae のヒト歯肉上皮細胞への感染経路が解析され、併せて線毛の歯周病発症における役割を解明した。これらの成果をもとに P. gulae 感染と歯周病発症の関連性が明らかとなり、人獣共通感染症としての歯周疾患の治療法・予防法開発へと繋げる狙いがある。

Research Products

• [Journal Article] Inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha (2020)
  • Author(s): Nomura R*, Inaba H*, Yasuda H*, Shirai M, Kato Y, Murakami M, Iwashita N, Shirahata S, Yoshida S, Matayoshi S, Yasuda J, Arai N, Asai F, Matsumoto-Nakano M, Nakano K. (*Contributed equally)
  • Journal Title: Scientific reports Volume: 22 Issue: 12
  • DOI: 10.1111/cmi.13254
  • Peer Reviewed / Open Access
• [Journal Article] Inhibitory effect of a mouth rinse formulated with chlorhexidine gluconate, ethanol, and green tea extract against major oral bacterial species (2020)
  • Author(s): Nomura, R., Inaba, H., Matayoshi, S., Yoshida, S., Matsumi, Y., Matsumoto-Nakano, M., Nakano, K
  • Journal Title: Journal of Oral Science Volume: 62 Issue: 2 Pages: 206-211
  • DOI: 10.2334/josnusd.18-0483
  • NAID: 130007821416
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha (2020)
  • Author(s): Nomura, R.*, Inaba, H.*, Yasuda, H.*, Shirai, M., Kato, Y., Murakami, M., Iwashita, N., Shirahata, S., Yoshida, S., Matayoshi, S., Yasuda, J., Arai, N., Asai, F., Matsumoto-Nakano, M., Nakano, K. (*contributed equally to authors)
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 3113-3113
  • DOI: 10.1038/s41598-020-59730-9
  • Peer Reviewed / Open Access
• [Presentation] Porphyromonas gulae プロテアーゼによる歯肉上皮細胞傷害能の評価 (2020)
  • Author(s): 吉田 翔
  • Organizer: 第58回日本小児歯科学会大会