Symbiotic relationship of endogenous bacteria including pathogens for infectious disease development in ticks

• Project/Area Number: 17K08835
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: University of Shizuoka
• Principal Investigator: OHASHI NORIO 静岡県立大学, 食品栄養科学部, 教授 (10169039)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Rickettsia japonica / Japanese spotted fever / Rickettsia sp. LON / Rickettsia sp. G4 / Coxiella-like symbiont / Haemaphysalis / Tick / Rickettsia / マダニ / Coxiella様共生細菌 / 感染症 / 日本紅斑熱 / リケッチア / L929 / THP-1 / 共生細菌 / 生殖系統 / 両性生殖 / 単為生殖 / メタ16S解析 / 細菌 / 生態学 / 微生物

Outline of Final Research Achievements

Rickettsia japonica that causes Japanese spotted fever, nonpathogenic rickettsiae, and Coxiella-like symbionts (CLE) are a group of endogenous bacteria in ticks. It is known that these bacteria are passed on to the tick's offspring by vertical transmission. We found that (i) the nonpathogenic Rickettsia sp. LON harbored by Haemaphysalis longicornis ticks becomes absent in ticks with the unique parthenogenetic reproductive system, (ii) pathogenic R. japonica and nonpathogenic Rickettsia sp. G4 possessed by Haemaphysalis histricis ticks are both a copy number of 100-1,000,000 per tick, (iii) Haemaphysalis tick species and CLE species are co-evolved, and (iv) 4 out of 24 haplotypes of H. histricis ticks possess pathogenic R. japonica. These results are expected to contribute greatly to the control of tick-borne infectious diseases in Japan in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義としては、(i) 日本紅斑熱を引き起こすリケッチア(Rj)のマダニ内のコピー数を明らかにしたこと、(ii) マダニ内の病原性Rjと非病原性R-G4を識別できる検出法を開発したこと、(iii) 単為生殖系のマダニではリケッチアが消えていくことを見出したこと、(iv) マダニ種とCLE種が共種分化していることを発見したこと、(v) マダニのあるハプロタイプが病原性Rjを保有していることが判ったこと、などである。社会的意義としては、公衆衛生上、日本紅斑熱の多発地域での啓発活動に役立つ知見が得られたことと考える。

Research Products

• [Journal Article] A Case of Human Granulocytic Anaplasmosis Suspected to be Complicated by Cholangitis (2022)
  • Author(s): KAWAKAMI Manri、IKEDA Fusao、FUJIOKA Shinichi、FUJITA Hiromi、KIDA Koji、OHASHI Norio
  • Journal Title: Kansenshogaku Zasshi Volume: 96 Issue: 1 Pages: 29-33
  • DOI: 10.11150/kansenshogakuzasshi.96.29
  • NAID: 130008145404
  • ISSN: 0387-5911, 1884-569X
  • Year and Date: 2022-01-20
  • Peer Reviewed
• [Journal Article] Growth Characteristics of <i>Rickettsia</i> Species LON Strains Closely Related to <i>Rickettsia</i> <i>japonica</i> Isolated from <i>Haemaphysalis longicornis</i> Ticks in Mouse Derived L929 and Human-Derived THP-1 Host Cell Lines (2021)
  • Author(s): Tai H, Su H, Takamoto N, Fujita H, Takano A, Oishi S, Abe F, Ando S, Ohashi N.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 74 Issue: 2 Pages: 102-109
  • DOI: 10.7883/yoken.JJID.2020.444
  • NAID: 130008002351
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2021-03-31
  • Peer Reviewed / Open Access
• [Journal Article] Surveillance of Borrelia miyamotoi-carrying ticks and genomic analysis of isolates in Inner Mongolia, China (2021)
  • Author(s): Gaowa、Wulantuya、Sato Kozue、Liu Dan、Cui Yunhong、Yin Xuhong、Zhang Lihua、Li Hong、Wang Tingfu、Liu Rongxin、Wu Lijing、Lu Saixia、Gao Ting、Zhang Zitong、Cao Minzhi、Wang Guodong、Li Chunpu、Yan Dacheng、Ohashi Norio、Ando Shuji、Kawabata Hiroki
  • Journal Title: Parasites & Vectors Volume: 14 Issue: 1 Pages: 368-368
  • DOI: 10.1186/s13071-021-04809-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diversity unearthed by estimated molecular phylogeny and ecologically quantitative characteristics of uncultured Ehrlichia bacteria in Haemaphysalis ticks, Japan. (2021)
  • Author(s): Su H, Onoda E, Tai H, Fujita H, Sakabe S, Azuma K, Akachi S, Oishi S, Abe F, Ando S, Ohashi N.
  • Journal Title: Sci Rep. Volume: 11 Issue: 1 Pages: 687-687
  • DOI: 10.1038/s41598-020-80690-7
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular proliferation of Anaplasma phagocytophilum is promoted via modulation of endoplasmic reticulum stress signaling in host cells (2020)
  • Author(s): Yoshikawa Y, Sugimoto K, Ochiai Y, Ohashi N.
  • Journal Title: Microbiol Immunol. Volume: 64 Issue: 4 Pages: 70-279
  • DOI: 10.1111/1348-0421.12770
  • Peer Reviewed
• [Journal Article] Predominant Shift of Different P44-Expressing <i>Anaplasma phagocytophilum</i> in Infected HL-60, THP-1, NB4, and RF/6A Cell Lines (2019)
  • Author(s): Shimada M, Takamoto N, Su H, Sasahara H, Shimamura Y, Ando S, Ohashi N.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 72 Issue: 2 Pages: 73-80
  • DOI: 10.7883/yoken.JJID.2018.230
  • NAID: 130007620385
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2019-03-31
  • Peer Reviewed / Open Access
• [Journal Article] Insight of diagnostic performance using B-cell epitope antigens derived from triple P44-related proteins of Anaplasma phagocytophilum (2019)
  • Author(s): 1.Su H, Ito K, Kawarasaki Y, Morita H, Nose H, Ikeda K, Nakadouzono F, Gokuden M, Kamiyama S, Tokaji A, Rikitake Y, Kawaguchi T, Umekita K, Oishi S, Abe F, Kanda T, Kawabata H, Ando S, Ohashi N.
  • Journal Title: Diagn Microbiol Infect Dis. Volume: 95 Issue: 2 Pages: 125-130
  • DOI: 10.1016/j.diagmicrobio.2019.05.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular Detection and Characterization of <i>p44</i>/<i>msp2</i> Multigene Family of <i>Anaplasma phagocytophilum</i> from <i>Haemaphysalis longicornis</i> in Mie Prefecture, Japan (2019)
  • Author(s): 2.Su H, Sato A, Onoda E, Fujita H, Sakabe S, Akachi S, Oishi S, Abe F, Kanda T, Shimamura Y, Masuda S, Ohashi N.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 72 Issue: 3 Pages: 199-202
  • DOI: 10.7883/yoken.JJID.2018.485
  • NAID: 130007652450
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Isolation and molecular detection of Ehrlichia species from ticks in western, central, and eastern Japan (2019)
  • Author(s): Taira M, Kadosaka T, Sato H, Ohashi N, Fujita H, Saijo M, Monma N, Ando S, Kawabata H.
  • Journal Title: Tick Tick Borne Dis. Volume: 10 Issue: 2 Pages: 344-351
  • DOI: 10.1016/j.ttbdis.2018.11.010
  • Peer Reviewed
• [Journal Article] Evaluation of Diagnostic Assay for Rickettsioses Using Duplex Real-Time PCR in Multiple Laboratories in Japan (2018)
  • Author(s): Kawamori F, Shimazu Y, Sato H, Monma N, Ikegaya A, Yamamoto S, Fujita H, Morita H, Tamaki Y, Takamoto N, Su H, Shimada S, Shimamura Y, Masuda S, Ando S, Ohashi N
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 71 Issue: 4 Pages: 267-273
  • DOI: 10.7883/yoken.JJID.2017.447
  • NAID: 130007418376
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2018-07-31
  • Peer Reviewed / Open Access
• [Journal Article] Spotted fever group Rickettsia in Inner Mongolia, China, 2015-2016. (2018)
  • Author(s): Gaowa, Wulantuya, Yin X, Guo S, Ding C, Cao M, Kawabata H, Sato K, Ando S, Fujita H, Kawamori F, Su H, Shimada M, Shimamura Y, Masuda S, Ohashi N.
  • Journal Title: Emerg. Infect. Dis. Volume: 24 Issue: 11 Pages: 2105-2107
  • DOI: 10.3201/eid2411.162094
  • Peer Reviewed / Open Access
• [Journal Article] Tomato saponin supplementation ameliorates the development of experimental arthritis by regulating inflammatory responses (2018)
  • Author(s): Yoshikawa Y, Katayanagi Y, Kamiya M, Yamamoto Y, Fukutomi R, Imai S, Miyoshi N, Ohashi N.
  • Journal Title: J. Funct. Foods Volume: 49 Pages: 458-464
  • DOI: 10.1016/j.jff.2018.09.009
  • Peer Reviewed
• [Journal Article] Case of Human Infection with <i>Anaplasma phagocytophilum</i> in Inner Mongolia, China (2018)
  • Author(s): Gaowa, Wulantuya, Yin X, Cao M, Guo S, Ding C, Lu Y, Luo J, Kawabata H, Ando S, Su H, Shimada M, Takamoto N, Shimamura Y, Masuda S, Ohashi N
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 71 Issue: 2 Pages: 155-157
  • DOI: 10.7883/yoken.JJID.2017.450
  • NAID: 130006517093
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Case report: Clinical features of a case of suspected Borrelia miyamotoi disease in Hokkaido, Japan (2017)
  • Author(s): Yamano K, Ito T, Kiyanagi K, Yamazaki H, Sugawara M, Saito T, Ohashi N, Zamoto-Niikura A, Sato K, Kawabata H.
  • Journal Title: Am. J. Trop. Med. Hyg. Volume: 97 Issue: 1 Pages: 84-87
  • DOI: 10.4269/ajtmh.16-0699
  • Peer Reviewed
• [Journal Article] Inhibitory effects of food additives derived from polyphenols on staphylococcal enterotoxin A production and biofilm formation by Staphylococcus aureus. (2017)
  • Author(s): Shimamura Y, Hirai C, Sugiyama Y, Shibata M, Ozaki J, Murata M, Ohashi N, Masuda S.
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 81(12) Issue: 12 Pages: 2346-2352
  • DOI: 10.1080/09168451.2017.1395681
  • Peer Reviewed / Open Access
• [Presentation] Multilocus sequence typing of Ehrlichia species detected from ticks in Japan (2020)
  • Author(s): 3.蘇泓如，小野田瑛厘，坂部茂俊，赤字重宏，藤田博己，大石沙織，阿部冬樹，神田隆，大橋典男
  • Organizer: 第93回日本細菌学会総会
• [Presentation] マダニ内のRickettsia japonicaと非病原性Rickettsiaの識別検出 (2020)
  • Author(s): 4.小野田瑛厘，蘇泓如，坂部茂俊，赤字重宏，藤田博己，大石沙織，阿部冬樹，神田隆，大橋典男
  • Organizer: 第93回日本細菌学会総会
• [Presentation] フタトゲチマダニが保有するアナプラズマ属細菌について (2019)
  • Author(s): 1.蘇泓如，小野田瑛厘，坂部茂俊，赤字重宏，大石沙織，阿部冬樹，神田隆，大橋典男
  • Organizer: 第27回ダニと疾患のインタフェースに関するセミナー（SADI）天草大会
• [Presentation] マダニに内在する日本紅斑熱リケッチアの高感度検出法の検討について (2019)
  • Author(s): 2.小野田瑛厘，蘇泓如，坂部茂俊，赤地重宏，大石沙織，阿部冬樹，神田隆，大橋典男
  • Organizer: 第27回ダニと疾患のインタフェースに関するセミナー（SADI）天草大会
• [Presentation] マダニに内在するRickettsia japonicaの高感度・特異検出法の検討 (2018)
  • Author(s): 小野田瑛厘，佐藤綾香，蘇泓如，藤田博己，坂部茂俊，赤地重宏，大石沙織，阿部冬樹，神田隆，島村裕子，増田修一，大橋典男
  • Organizer: 第25回リケッチア研究会・第11回日本リケッチア症臨床研究会
• [Presentation] アナプラズマ症におけるペプチド抗原を用いた血清診断法へのアプローチ (2018)
  • Author(s): 蘇泓如，伊藤圭祐，佐藤綾香，大石沙織，阿部冬樹，神田隆，安藤修二，川端寛樹，大橋典男
  • Organizer: 第25回リケッチア研究会・第11回日本リケッチア症臨床研究会
• [Presentation] 同居家族の続発情報により遺伝子検出に至った日本紅斑熱陽性症例 (2018)
  • Author(s): 大石沙織，酒井悠希子，阿部冬樹，神田隆，大橋典男
  • Organizer: 第25回リケッチア研究会・第11回日本リケッチア症臨床研究会
• [Presentation] マダニ内在性細菌群のメタ16S解析から見るCoxiellaとRickettsia (2018)
  • Author(s): 佐藤綾香，高本直矢，高野愛，大石沙織，阿部冬樹，神田隆，平良雅克，藤田博己，島村裕子，大橋典男
  • Organizer: 第91回日本細菌学会総会（福岡）
• [Presentation] Anaplasma phagocytophilum in Japan (2017)
  • Author(s): Ohashi N, Gaowa, Wuritu, Wu D, Kawamori F, Su H, Shimada M, Takamoto N, Tai H, Ando S
  • Organizer: International Congress on Rickettsiae and other Intracellular Bacteria (Marseille, France)
  • Int'l Joint Research
• [Presentation] Rickettsia sp. LONの細胞内増殖評価法の検討 (2017)
  • Author(s): 1.田井仁，高本直矢，藤田博己，島田雅彦，蘇泓如，大橋典男
  • Organizer: 第24回リケッチア研究会 (東京)
• [Presentation] 単為生殖がもたらすダニ内在性リケッチアへの影響 (2017)
  • Author(s): 2.高本直矢，田井仁，佐藤寛子，平良雅克，高野愛，高田伸弘，川森文彦，池ヶ谷朝香，大石沙織，阿部冬樹，神田隆，藤田博己，大橋典男
  • Organizer: 第24回リケッチア研究会 (東京)
• [Presentation] マダニ内に存在する細菌叢のメタ16S解析 (2017)
  • Author(s): 3.佐藤綾香，高本直矢，笹原榛華，松﨑光ノ介，高野愛，大石沙織，阿部冬樹，神田隆，平良雅克，藤田博己，島村裕子，増田修一，大橋典男
  • Organizer: 第24回リケッチア研究会 (東京)
• [Book] 栄養科学イラストレイテッド「微生物学」 (2020)
  • Author(s): 大橋典男 他
  • Total Pages: 213
  • Publisher: 羊土社
  • ISBN: 9784758113588