Elucidation of pathogenic factor in Streptococcus mutans contributing to the stroke onset

• Project/Area Number: 19K10471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57080:Social dentistry-related
• Research Institution: Tsurumi University
• Principal Investigator: Murata Takatoshi 鶴見大学, 歯学部, 講師 (10313529)
• Co-Investigator(Kenkyū-buntansha): 花田 信弘 鶴見大学, 歯学部, 教授 (70180916) ; 宮之原 真由 鶴見大学, 歯学部, 学部助手 (70460186)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Streptococcus mutans / 脳卒中 / コラーゲン結合蛋白 / コラーゲン結合タンパク / グルコシルトランスフェラーゼ / 遺伝子ノックアウト / メンブランベシクル / cmn

Outline of Research at the Start

う蝕の原因菌であるStreptococcus mutansの感染と脳卒中発症との関連が報告されている。しかしながら、菌体そのものは脳血液関門を通過することができないので、菌体が直接脳卒中発症に関与しているとは考えにくい。そこで、脳深部に到達することが可能なS. mutansから放出されるメンブランベシクルに焦点を当て、メンブランベシクルが脳出血による脳卒中発症能力を有するか評価し、「S. mutansが脳卒中発症予防の標的となり得るか？」その可能性を検証する。

Outline of Final Research Achievements

It has been reported that an association between infection with Streptococcus mutans expressing collagen-binding protein (CNM) and stroke onset. It is possible that the virulence factor that contributes to the onset of stroke is not the cells themselves, but the extracellularly secreted or leaked CNM because of no reports of isolation of S. mutans cells from stroke-affected areas.
CNM is a protein with a molecular weight of 70 kDa that strongly adheres to the cell wall and is present on the surface of the bacterial bodies. However, it has been revealed that CNM detected outside the bacterial bodies has a molecular weight of approximately 100 kDa. Therefore, this suggests the possibility that CNM complexes, which are bound to some unidentified molecules, may contribute to the onset of stroke.

Academic Significance and Societal Importance of the Research Achievements

我が国の疾病分類別医科診療医療費では、脳血管疾患を含む「循環器系の疾患」は最も多く約20%を占めている重大疾病である。そのような社会背景の中、脳血管疾患を含む生活習慣病の発症予防、重症化予防の基本方針として、「歯と口腔の健康」の推進が定められている。
本研究成果は、代表的な口腔病原性細菌であるStreptococcus mutansの脳卒中発症に寄与する病原因子を示唆するものであり、脳卒中発症予防における「歯と口腔の健康」の推進の妥当性を支持する。また、今後の研究展開により、S. mutansによる脳卒中発症メカニズム解明、S. mutansを標的とする脳卒中発症予防法の開発につながる。

Research Products

• [Journal Article] Effect of advanced periodontal self-care in patients with early-stage periodontal diseases on endothelial function: An open-label, randomized controlled trial (2021)
  • Author(s): Okada Ayako、Murata Takatoshi、Matin Khairul、Ariyoshi Meu、Otsuka Ryoko、Yamashita Mamiko、Suzuki Masayuki、Wakiyama Rumi、Tateno Ken、Suzuki Megumi、Aoyagi Hitomi、Uematsu Hiromi、Imamura Akiko、Kosaka Miki、Mizukaki Tomoko、Sato Tsutomu、Kawahara Hiroshi、Hanada Nobuhiro
  • Journal Title: PLOS ONE Volume: 16 Issue: 9 Pages: 0257247-0257247
  • DOI: 10.1371/journal.pone.0257247
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibitory effect of black cumin (Nigella sativa) seed essential oil on Fusobacterium nucleatum L-methionine-γ-lyase (L-methioninase) activity (2021)
  • Author(s): Ishikawa Masao、Murata Takatoshi、Okamoto Masaaki、Miyanohara Mayu、Yamashita Mamiko、Hanada Nobuhiro、Senpuku Hidenobu、Shibuya Koji
  • Journal Title: FEMS Microbiology Letters Volume: 368 Issue: 7 Pages: 1-5
  • DOI: 10.1093/femsle/fnab041
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oxidized Low-Density Lipoprotein Promotes In Vitro Calcification (2020)
  • Author(s): Yamashita Mamiko、Nomura Yoshiaki、Ishikawa Misao、Shimoda Shinji、Hanada Nobuhiro
  • Journal Title: Materials Volume: 13 Issue: 22 Pages: 5120-5120
  • DOI: 10.3390/ma13225120
  • Peer Reviewed / Open Access
• [Journal Article] Nutritional Status and Oral Frailty: A Community Based Study (2020)
  • Author(s): Nomura Yoshiaki、Ishii Yoshimasa、Suzuki Shunsuke、Morita Kenji、Suzuki Akira、Suzuki Senichi、Tanabe Joji、Ishiwata Yasuo、Yamakawa Koji、Chiba Yota、Ishikawa Meu、Sogabe Kaoru、Kakuta Erika、Okada Ayako、Otsuka Ryoko、Hanada Nobuhiro
  • Journal Title: Nutrients Volume: 12 Issue: 9 Pages: 2886-2886
  • DOI: 10.3390/nu12092886
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Supplied Food Consistency and Oral Functions of Institutionalized Elderly (2020)
  • Author(s): Nomura Y, Tsutsumi I, Nagasaki M, Tsuda H, Koga F, Kashima N, Uraguchi M, Okada A, Kakuta E, Hanada N.
  • Journal Title: Int J Dent. Volume: 2020 Pages: 3463056-3463056
  • DOI: 10.1155/2020/3463056
  • Peer Reviewed / Open Access
• [Journal Article] Oral Microbiome of Children Living in an Isolated Area in Myanmar (2020)
  • Author(s): Nomura Y, Otsuka R, Hasegawa R, Hanada N.
  • Journal Title: Int J Environ Res Public Health. Volume: 5;17(11) Issue: 11 Pages: 4033-4033
  • DOI: 10.3390/ijerph17114033
  • Peer Reviewed / Open Access
• [Journal Article] Workforce and Contents of Home Dental Care in Japanese Insurance System (2020)
  • Author(s): Nomura Yoshiaki、Okada Ayako、Kakuta Erika、Otsuka Ryoko、Saito Hideaki、Maekawa Hiroshi、Daikoku Hideki、Hanada Nobuhiro、Sato Tamotsu
  • Journal Title: International Journal of Dentistry Volume: 2020 Pages: 1-6
  • DOI: 10.1155/2020/7316796
  • Peer Reviewed / Open Access
• [Journal Article] Prioritization of the Skills to Be Mastered for the Daily Jobs of Japanese Dental Hygienists (2020)
  • Author(s): Nomura Yoshiaki、Kakuta Erika、Okada Ayako、Yamamoto Yuko、Tomonari Hiroshi、Hosoya Noriyasu、Hanada Nobuhiro、Yoshida Naomi、Takei Noriko
  • Journal Title: International Journal of Dentistry Volume: 2020 Pages: 1-8
  • DOI: 10.1155/2020/4297646
  • Peer Reviewed / Open Access
• [Journal Article] Properties of manual toothbrush that influence on plaque removal of interproximal surface in?vitro (2020)
  • Author(s): Otsuka R, Nomura Y, Okada A, Uematsu H, Nakano M, Hikiji K, Hanada N, Momoi Y
  • Journal Title: J Dent Sci Volume: 15 Issue: 1 Pages: 14-21
  • DOI: 10.1016/j.jds.2019.07.005
  • Peer Reviewed / Open Access
• [Journal Article] Tooth-Level Analysis of Dental Caries in Primary Dentition in Myanmar Children (2020)
  • Author(s): Nomura Yoshiaki、Otsuka Ryoko、Wint Wit Yee、Okada Ayako、Hasegawa Ryo、Hanada Nobuhiro
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 17 Issue: 20 Pages: 7613-7613
  • DOI: 10.3390/ijerph17207613
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk factors for postoperative pneumonia according to examination findings before surgery under general anesthesia (2020)
  • Author(s): Yuko Inai , Yoshiaki Nomura , Tohru Takarada , Nobuhiro Hanada , Naohisa Wada
  • Journal Title: Clinical oral investigations Volume: Epub ahead of print Issue: 10 Pages: 3577-3585
  • DOI: 10.1007/s00784-020-03230-7
  • Peer Reviewed / Open Access
• [Journal Article] Dental Hygienists’ Practice in Perioperative Oral Care Management According to the Japanese Dental Hygienists Survey 2019 (2020)
  • Author(s): Nomura Yoshiaki、Ohara Yuki、Yamamoto Yuko、Okada Ayako、Hosoya Noriyasu、Hanada Nobuhiro、Takei Noriko
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 18 Issue: 1 Pages: 114-114
  • DOI: 10.3390/ijerph18010114
  • Peer Reviewed / Open Access
• [Journal Article] Optimal Examination Sites for Periodontal Disease Evaluation: Applying the Item Response Theory Graded Response Model (2020)
  • Author(s): Nomura Y, Morozumi T*, Fukuda M, Hanada N, Kakuta E, Kobayashi H, Minabe M, Nakamura T, Nakayama Y, Nishimura F, Noguchi K, Numabe Y, Ogata Y, Saito A, Sato S, Sekino S, Sugano N, Sugaya T, Suzuki F, Takahashi K, Takai H, Takashiba S, Umeda M, Yoshie H, Yoshimura A, Yoshinari N, Nakagawa T
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 11 Pages: 3754-3754
  • DOI: 10.3390/jcm9113754
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Mucosal Brushing on the Serum Levels of C-Reactive Protein for Patients Hospitalized with Acute Symptoms (2020)
  • Author(s): Nakahodo Naoko、Nomura Yoshiaki、Oshiro Takumi、Otsuka Ryoko、Kakuta Erika、Okada Ayako、Inai Yuko、Takei Noriko、Hanada Nobuhiro
  • Journal Title: Medicina Volume: 56 Issue: 10 Pages: 549-549
  • DOI: 10.3390/medicina56100549
  • Peer Reviewed / Open Access
• [Journal Article] Safety Assessment of the Candidate Oral Probiotic Lactobacillus Crispatus YIT 12319: Analysis of Antibiotic Resistance and Virulence-Associated Genes (2020)
  • Author(s): Terai T, Kato K, Ishikawa E, Nakao M, Ito M, Miyazaki K, Kushiro A, Imai S, Nomura Y, Hanada N, Okumura T.
  • Journal Title: Food Chem Toxicol. Volume: 140: Pages: 111278-111278
  • DOI: 10.1016/j.fct.2020.111278
  • Peer Reviewed / Open Access
• [Journal Article] Effects of self-assessed chewing ability, tooth loss and serum albumin on mortality in 80-year-old individuals: a 20-year follow-up study (2020)
  • Author(s): Nomura Yoshiaki、Kakuta Erika、Okada Ayako、Otsuka Ryoko、Shimada Mieko、Tomizawa Yasuko、Taguchi Chieko、Arikawa Kazumune、Daikoku Hideki、Sato Tamotsu、Hanada Nobuhiro
  • Journal Title: BMC Oral Health Volume: 20 Issue: 1 Pages: 122-122
  • DOI: 10.1186/s12903-020-01113-7
  • Peer Reviewed / Open Access
• [Journal Article] Mortality- and Health-Related Factors in a Community-Dwelling of Oldest-Older Adults at the Age of 90: A 10-Year Follow-Up Study (2020)
  • Author(s): Nomura Yoshiaki、Shimada Mieko、Kakuta Erika、Okada Ayako、Otsuka Ryoko、Tomizawa Yasuko、Taguchi Chieko、Arikawa Kazumune、Daikoku Hideki、Sato Tamotsu、Hanada Nobuhiro
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 17 Issue: 24 Pages: 9584-9584
  • DOI: 10.3390/ijerph17249584
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the Serum Level of Albumin and Self-Assessed Chewing Ability on Mortality, QOL, and ADLs for Community-Dwelling Older Adults at the Age of 85: A 15 Year Follow up Study (2020)
  • Author(s): Nomura Yoshiaki、Kakuta Erika、Okada Ayako、Otsuka Ryoko、Shimada Mieko、Tomizawa Yasuko、Taguchi Chieko、Arikawa Kazumune、Daikoku Hideki、Sato Tamotsu、Hanada Nobuhiro
  • Journal Title: Nutrients Volume: 12 Issue: 11 Pages: 3315-3315
  • DOI: 10.3390/nu12113315
  • Peer Reviewed / Open Access
• [Journal Article] Purification of a High Molecular Mass Protein in Streptococcus mutans. (2019)
  • Author(s): Murata T , Yamashita M , Ishikawa M , Shibuya K , Hanada N
  • Journal Title: Journal of visualized experiments : JoVE Volume: 151 Issue: 151 Pages: 151-151
  • DOI: 10.3791/59804
  • Peer Reviewed / Open Access
• [Journal Article] Consistency of supplied food and dentition status of the elderly in residential care homes. (2019)
  • Author(s): Nomura Y , Okada A , Kakuta E , Otsuka R , Sogabe K , Yamane K , Yamamoto T , Shigeta Y , Shigemoto S , Ogawa T , Hanada N
  • Journal Title: BMC Oral Health Volume: 19 Issue: 1 Pages: 74-74
  • DOI: 10.1186/s12903-019-0770-0
  • Peer Reviewed / Open Access
• [Journal Article] Smoking and periodontal microorganisms (2019)
  • Author(s): Hanioka T, Morita M, Yamamoto T, Inagaki K, Wang P-L, Ito H, Morozumi T, Takeshita T, Suzuki N, Shigeishi H, Sugiyama M, Ohta K, Nagao T, Hanada N, Ojima M, Ogawa H
  • Journal Title: The Japanese Dental Science Review Volume: 55 Issue: 1 Pages: 88-94
  • DOI: 10.1016/j.jdsr.2019.03.002
  • NAID: 50014414225
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevalence of Dental Caries in 5- and 6-Year-Old Myanmar Children. (2019)
  • Author(s): Nomura Y , Maung K , Kay Khine EM , Sint KM , Lin MP , Win Myint MK , Aung T , Sogabe K , Otsuka R , Okada A , Kakuta E , Wint WY , Uraguchi M , Hasegawa R , Hanada N
  • Journal Title: International journal of dentistry Volume: 2019 Pages: 5948379-5948379
  • DOI: 10.1155/2019/5948379
  • Peer Reviewed / Open Access
• [Journal Article] PRECEDE-PROCEED model based questionnaire and saliva tests for oral health checkup in adult (2019)
  • Author(s): Nomura Y , Matsuyama T , Fukai K , Okada A , Ida M , Yamauchi N , Hanamura H , Yabuki Y , Watanabe K , Sugawara M , Imanishi Y , Koizumi N , Murano Y , Nishiyama A , Fukukawa Y , Otsuka R , Hanada N
  • Journal Title: Journal of Oral Science Volume: 61 Issue: 4 Pages: 544-548
  • DOI: 10.2334/josnusd.18-0288
  • NAID: 130007751518
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Presentation] 高純度次亜塩素酸水の病原性口腔微生物に対する効果 (2023)
  • Author(s): 村田貴俊、井上一彦、佐藤 勉、菊地憲次、堀田国元、吉川敏一
  • Organizer: 第24回日本口腔機能水学会総会・学術大会
• [Presentation] Helicobacter pyloriとStreptococcus mutansとの共培養時の超微形態学的特徴 (2023)
  • Author(s): 山下万美子、田中とも子、堀江哲郎、村田貴俊、荒木萌花、福田雅臣
  • Organizer: 第72回日本口腔衛生学会・学術大会
• [Presentation] 口腔清掃にTHP 3DS pasteを併用したカンジダの除菌効果 (2023)
  • Author(s): 宮之原真由、影島宏紀、山田秀則、花田信弘、村田貴俊
  • Organizer: 第72回日本口腔衛生学会・学術大会
• [Presentation] 全身的な健康を歯科から考える”予防医学”としての概念を歯科へ「3DS除菌外来」の試み 第九報 (2023)
  • Author(s): 山田秀則、宮之原真由、村田貴俊、岡田彩子、花田信弘
  • Organizer: 第72回日本口腔衛生学会・学術大会
• [Presentation] 菌体外で検出されるStreptococcus mutansコラーゲン結合タンパク（Cnm）複合体 (2022)
  • Author(s): 村田貴俊
  • Organizer: 第64回歯科基礎医学会学術大会
• [Presentation] 口腔カンジダ検出における唾液と舌苔の比較 (2020)
  • Author(s): 宮之原真由、村田貴俊、岡本公彰、山田秀則、岩本康平、山下万美子、野村義明、花田信弘
  • Organizer: 第69回日本口腔衛生学会・総会
• [Presentation] 酸化LDLによる根面う蝕予防 (2020)
  • Author(s): 山下万美子、野村義明、村田貴俊、岡田彩子、広田一男、石川美紗緒、下田信治、花田信弘
  • Organizer: 第69回日本口腔衛生学会・総会
• [Presentation] 血管内皮機能に対する歯周組織健康状態改善の有効性評価（第３報）：ランダム化並行群間試験 (2020)
  • Author(s): 岡田彩子、村田貴俊、有吉芽生、大塚良子、山下万美子、小坂美樹、鈴木 恵、赤間ひとみ、植松裕美、今村安芸子、佐藤 勉、マティン カイルール、花田信弘
  • Organizer: 第69回日本口腔衛生学会・総会
• [Presentation] 全身的な健康を歯科から考える予防医学としての概念を歯科へ「3DS除菌外来」の試み 第七報 (2020)
  • Author(s): 山田秀則、宮之原真由、曽我部薫、岡田彩子、武内博朗、村田貴俊、野村義明、花田信弘
  • Organizer: 第69回日本口腔衛生学会・総会
• [Presentation] ブラッククミンおよび殺菌剤のカンジダに対する抗真菌活性について (2019)
  • Author(s): 石川正夫、村田貴俊、岡本公彰、泉福英信、花田信弘、渋谷耕司
  • Organizer: 第68回日本口腔衛生学会・総会
• [Presentation] 血管内皮機能に対する歯周組織健康状態改善の有効性評価：ランダム化並行群間試験 (2019)
  • Author(s): 岡田彩子、村田貴俊、有吉芽生、大塚良子、山下万美子、鈴木恵、青柳ひとみ、植松裕美、今村安芸子、佐藤勉、マティン カイルール、花田信弘
  • Organizer: 第68回日本口腔衛生学会・総会
• [Presentation] 全身的な健康を歯科から考える”予防医学”としての概念を歯科へ「3DS除菌外来」の試み (2019)
  • Author(s): 山田秀則、宮之原真由、大塚良子、石川芽生、曾我部薫、岡田彩子、武内博朗、村田貴俊、野村義明、花田信弘
  • Organizer: 第68回日本口腔衛生学会・総会
• [Book] 公衆衛生学 (2023)
  • Author(s): 網中雅仁、清原康介、熊田 薫、後藤政幸、古屋博行、村田貴俊、本橋隆子、依田健志
  • Total Pages: 308
  • Publisher: 理工図書株式会社
  • ISBN: 9784844609278