Systematic re-estimation of polymorphism of T. pallidum genome from wider range of specimens including T. p DNA of lower copy numbers

• Project/Area Number: 18K09184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Nakayama Shu-ichi 国立感染症研究所, 細菌第一部, 主任研究官 (80280767)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 近縁株を細分化できる１塩基置換候補 / 詳細な菌株系統解析 / MSMとheterosexuals / 近縁系統株を細分可能なSNP / 国内株初のトレポネーマ全ゲノム解析 / 梅毒トレポネーマ / 疫学 / 分子型別 / 全ゲノム情報 / 患者性指向 / ゲノム多様性 / 流行型把握 / 分子型別改良

Outline of Final Research Achievements

Among the T.pallidum strains detected in Japan during 2017, the macrolide resistant strain type 14d/f was found in significantly more cases of syphilis among heterosexuals than in those among men who have sex with men (MSM); i.e., 79% (31/39) of the strains from heterosexuals were 14d/f compared to 37% (7/19) of those from MSM. In addition, 83% (50/60) of the strains were identified as macrolide resistant. 90% (35/39) of the strains from heterosexuals were macrolide resistant compared to 58% (11/19) of those from MSM.
The whole genome sequencing analyses using the strains detected between 2014 and 2018 in Japan showed that these strains were closely related to reported strains in China. However, those strains in these countries evolved independently after diverging from their most recent common ancestor. The genetic difference between the strains in these countries was characterized by single-nucleotide-polymorphism analyses of their penicillin binding protein genes.

Academic Significance and Societal Importance of the Research Achievements

性感染症の制御においては、科学的根拠に立脚したリスクグループごとへの介入がとくに重要である。この観点で今回、分子型別、全ゲノム解析結果ともでMSMとheterosexualsとが基本的には互いに分離できるコミュニティであることが示された意義は大きい。
全ゲノム解析から抽出された、近縁関係にある日本、中国株を細分できる一塩基置換候補は、近隣国からの輸入例を簡便に検出するマーカーツールとして活用できる可能性があり、今後は今回の全ゲノム解析には成功しなかった検体を含め、この塩基置換の有無を網羅的に解析し、まずその有用性を確定させることが重要であることが示された。

Research Products

• [Journal Article] Phylogenetic and Genetic Characterization of Treponema pallidum Strains from Syphilis Patients in Japan by Whole-genome Sequence Analysis from Global Perspectives. (2021)
  • Author(s): Nishiki, S., Lee, K., Kanai, M., Nakayama, S., and Ohnishi, M.
  • Journal Title: Sci. Rep. Volume: 11 Issue: 1 Pages: 3154-3154
  • DOI: 10.1038/s41598-021-82337-7
  • Peer Reviewed / Open Access
• [Journal Article] A novel peptide nucleic acid- and loop-mediated isothermal amplification assay for the detection of mutations in the 23S rRNA gene of Treponema pallidum (2020)
  • Author(s): Tarumoto Norihito、Imai Kazuo、Nakayama Shu-ichi、Itoda Ichiro、Sakai Jun、Murakami Takashi、Maesaki Shigefumi、Hayakawa Satoshi、Ohnishi Makoto、Maeda Takuya
  • Journal Title: Journal of Medical Microbiology Volume: 69 Issue: 12 Pages: 1339-1345
  • DOI: 10.1099/jmm.0.001275
  • Peer Reviewed
• [Journal Article] Epidemiology, Molecular Strain Types, and Macrolide Resistance of Treponema pallidum in Japan, 2017-2018. (2020)
  • Author(s): Nishiki, S., Arima, Y., Kanai, M., Shimuta, K., Nakayama, S., and Ohnishi
  • Journal Title: J. Infect. Chemother. Volume: 26 Issue: 10 Pages: 1042-1047
  • DOI: 10.1016/j.jiac.2020.05.022
  • Peer Reviewed
• [Journal Article] Molecular typing and macrolide resistance analyses of Treponema pallidum in heterosexuals and men who have sex with men in Japan, 2017. (2019)
  • Author(s): Kanai, M., Arima, Y., Nishiki, S., Shimuta, K., Itoda, I., Matsui, T., Oishi, K., Ohnishi, M, and Nakayama, S.
  • Journal Title: J. Clin. Microbiol. Volume: 57 Issue: 1
  • DOI: 10.1128/jcm.01167-18
  • Peer Reviewed / Open Access
• [Journal Article] Infective endocarditis due to Treponema pallidum: A case diagnosed by polymerase chain reaction analysis of aortic valve. (2019)
  • Author(s): Hijikata, S., Hongo, I., Nakayama, S., Yamaguchi, T., Sekikawa, Y., and Nozato, T.
  • Journal Title: Canadian Journal of Cardiology. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Cerebral Syphilitic Gumma can arise within months of reinfection: a case of histologically proven Treponema pallidum Strain Type 14b/f infection with Human Immunodeficiency Virus positivity. (2018)
  • Author(s): Y. Koizumi, T. Watabe, Y. Ota, S. Nakayama, N. Asai, M. Hagihara, Y. Yamagishi, H. Suematsu, T. Tsuzuki, M. Takayasu, M. Ohnishi, and H. Mikamo.
  • Journal Title: Sex Transm. Dis. Volume: 45
  • Peer Reviewed
• [Journal Article] Neisseria cinerea with high ceftriaxone MIC is a source of ceftriaxone and cefixime resistance-mediating penA sequences in Neisseria gonorrhoeae. (2018)
  • Author(s): Igawa, G., Yamagishi, Y., Dorin, M., Shimuta, K., Suematsu, H., Nakayama, S., Mikamo, H., Unemo, M., and Ohnishi, M.
  • Journal Title: Antimicrob. Agents Chemother. Volume: 62
  • Peer Reviewed / Open Access
• [Journal Article] Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages (2018)
  • Author(s): Yahara Koji、Nakayama Shu-ichi、Shimuta Ken、Lee Ken-ichi、Morita Masatomo、Kawahata Takuya、Kuroki Toshiro、Watanabe Yuko、Ohya Hitomi、Yasuda Mitsuru、Deguchi Takashi、Didelot Xavier、Ohnishi Makoto
  • Journal Title: Microbial Genomics Volume: 4 Issue: 8 Pages: 1-13
  • DOI: 10.1099/mgen.0.000205
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 比較的稀な分子型梅毒トレポネーマの短期間内での複数回検出例 (2019)
  • Author(s): 中山周一、井戸田一朗、大西 真
  • Organizer: 日本性感染症学会第31回学術大会
• [Presentation] PNA-LAMP法を用いたマクロライド耐性梅毒トレポネーマの検出に関する検討 (2019)
  • Author(s): 樽本憲人、前崎繁文、前田拓哉、中山周一、大西 真、早川 智、井戸田一朗
  • Organizer: 日本性感染症学会第31回学術大会
• [Presentation] 梅毒核酸検査における唾液やうがい液の有用性についての検討 (2019)
  • Author(s): 花岡 希、中山周一、尾上泰彦、錦 信吾、萬田和志、大西 真
  • Organizer: 日本性感染症学会第31回学術大会
• [Presentation] Infective endocarditis due to Treponema pallidum: A case diagnosed by polymerase chain reaction analysis of aortic valve. (2018)
  • Author(s): Hijikata, S., Hongo I., Nakayama, S., Sekikawa, Y., Iwai, T., Yamaguchi J., Sagawa, Y., Watanabe, K., Masuda, R., Miyazaki, R., Miwa, N., Hara, N., Yamaguchi, T., Nagata, Y., Nozato, T., and Hirano, K.
  • Organizer: The 82nd Annual Scientific Meeting of the Japanese Circulation Society.
• [Presentation] 梅毒の迅速診断の方向性―検査手技時間の短縮化と感染成立後陽性判定可能までのタイムラグの短縮化を目指す。 (2018)
  • Author(s): 中山周一
  • Organizer: 日本性感染症学会第31回学術大会。シンポジウム 1。
• [Presentation] 2015～2017年にわが国で分離された淋菌の薬剤感受性報告。 (2018)
  • Author(s): 安田 満、志牟田 健、中山周一、小林寅喆、大澤佳代、陳内理生、三宅啓文、濱砂良一、荒川創一、大西 真。
  • Organizer: 日本性感染症学会第31回学術大会。