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Elucidation of the drug-resistance acquisition mechanism in Mycobacterium tuberculosis to be multidrug and extremely-multidrug resistant and identification of those possible genetic markers.

Research Project

Project/Area Number 15K08724
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Epidemiology and preventive medicine
Research InstitutionHokkaido University

Principal Investigator

Nakajima Chie  北海道大学, 人獣共通感染症リサーチセンター, 准教授 (60435964)

Co-Investigator(Renkei-kenkyūsha) SUZUKI Yasuhiko  北海道大学, 人獣共通感染症リサーチセンター, 教授 (90206540)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords結核 / 多剤耐性 / 遺伝子解析 / 型別 / 疫学 / M. tuberculosis / 多剤耐性菌 / 全ゲノム解析
Outline of Final Research Achievements

Sequential acquisition of mutations in drug-resistance associating genes causes an emergence of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB). The Beijing genotype of MTB is known to be associating with MDR, and its prevalence among MDR-MTB population was significantly higher than that in non-MDR MTB in three TB high-burden countries; Myanmar, Nepal and Thailand. The majority of the Beijing type isolates belonged to the “modern” subtype and most of them had putative KatG S315T and RpsL K43R mutations suggesting those were isoniazid and streptomycin resistant. Those genetic characteristics can be used as a marker of transmissible MDR-MTB; thus, we have developed simple detection methods including a multiplex PCR to identify the “modern” type of the Beijing lineage and a line probe assay to diagnose isoniazid resistance.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (41 results)

All 2018 2017 2016 Other

All Int'l Joint Research (13 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (24 results) (of which Int'l Joint Research: 15 results,  Invited: 2 results)

  • [Int'l Joint Research] Department of Medical Research(ミャンマー)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] German Nepal Tuberculosis Project(ネパール)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Peradeniya University(スリランカ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] National Institute of Health(タイ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Zambia Teaching Hospital(ザンビア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Department of Medical Research(ミャンマー)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] German Nepal Tuberculosis Project(ネパール)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Peradeniya University(スリランカ)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] National Institute of Health(タイ)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Department of Medical Research(ミャンマー)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] German Nepal Tuberculosis Project(ネパール)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] National Institute of Health(タイ)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] ICDDR, B(バングラデシュ)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Genotypic characterization of pyrazinamide resistance in Mycobacterium tuberculosis isolated from Lusaka, Zambia2018

    • Author(s)
      Bwalya P, Yamaguchi T, Mulundu G, Nakajima C, Mbulo G, Solo ES, Fukushima Y, Kasakwa K, Suzuki Y.
    • Journal Title

      Tuberculosis (Edinb)

      Volume: 109 Pages: 117-122

    • DOI

      10.1016/j.tube.2017.12.007

    • NAID

      120006577375

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High diversity of multidrug resistant Mycobacterium tuberculosis Central Asian Strain isolates in Nepal2017

    • Author(s)
      Shah Y, Maharjan B, Thapa J, Poudel A, Diab HM, Pandey BD, Solo ES, Isoda N, Suzuki Y, Nakajima C
    • Journal Title

      Int J Infect Dis.

      Volume: 63 Pages: 13-20

    • DOI

      10.1016/j.ijid.2017.06.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genotypic diversity of Mycobacterium tuberculosis strains in Myanmar.2017

    • Author(s)
      Tun T, Aye KS, Nyunt WW, Crump JA, Nakajima C, Suzuki Y, Thinn KK, Cook GM, Aung HL.
    • Journal Title

      Infectious Diseases

      Volume: 49 Issue: 3 Pages: 237-239

    • DOI

      10.1080/23744235.2016.1231419

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Genotypic Characterization of Multi-drug-Resistant Mycobacterium tuberculosis isolates in Myanmar2016

    • Author(s)
      Aye KS, Nakajima C, Yamaguchi T, Win MM, Shwe MM, Win AA, Lwin T, Nyunt WW, Ti T, Suzuki Y.
    • Journal Title

      J Infect Chemother

      Volume: 22 Issue: 3 Pages: 174-179

    • DOI

      10.1016/j.jiac.2015.12.009

    • NAID

      120005981363

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Diverse molecular genotypes of Mycobacterium tuberculosis isolates circulating in Kandy, Sri Lanka2018

    • Author(s)
      C MENDIS, C RATNATUNGA, V THEVANESAM, A KUMARA, S WICKRAMASINGHE, D MADEGEDARA, C GAMAGE, C NAKAJIMA, Y SUZUKI
    • Organizer
      U.S.-Japan Cooperation Medical Science Program, 54nd Mycobacteria Panel Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of drug-resistant associated mutations in Mycobacterium tuberculosis isolates of Myanmar2018

    • Author(s)
      Nan Aye Thida Oo,Lai Lai San,Khin Saw Aye,Wah Wah Aung,中島 千絵,鈴木 定彦
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Evaluation of relationship between fluoroquinolone-resistance mutations and enzymic characters of DNA gyrase in non-PGG3 Mycobacterium tuberculosis2018

    • Author(s)
      Yuki Ouchi, Chie Nakajima, Yasuhiko Suzuki
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Insight into the Beijing genotype Mycobacterium tuberculosis in Myanmar2018

    • Author(s)
      Lai Lai San,Nan Aye Thida Oo,Wah Wah Aung,Khin Saw Aye,中島 千絵,鈴木 定彦
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Molecular diversity of Mycobacterium tuberculosis in Kandy, Sri Lanka: Insight to Beijing genotype2017

    • Author(s)
      Charitha MENDIS, Champa RATNATUNGA, Vasanthi THEVANESAM, Athula KUMARA, Susiji WICKRAMASINGHE, Dushantha MADEGEDARA, Chandika GAMAGE, Chie NAKAJIMA, Yasuhiko SUZUKI
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Molecular analysis of Streptomycin-resistance associating genes in Mycobacterium tuberculosis isolates from Nepal.2017

    • Author(s)
      Dipti SHRESTHA, Bhagwan MAHARJAN, Nan Aye Thida OO, Chie NAKAJIMA, Yasuhiko SUZUKI
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Impact of T95S and D668G in GyrA of Mycobacterium tuberculosis on compensatory evolution2017

    • Author(s)
      大内 勇樹,小出 健太郎,山口 智之,朴 鐘勲,金 玄,中島 千絵,鈴木 定彦
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Insight into the Beijing genotype Mycobacterium tuberculosis in Myanmar2017

    • Author(s)
      Lai Lai San, Nan Aye Thida Oo, Khin Saw Aye, Wah Wah Aung, Chie NAKAJIMA, Yasuhiko SUZUKI
    • Organizer
      第16回あわじしま感染症・免疫フォーラム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of pncA gene mutations in multidrug-resistant Mycobacterium tuberculosis isolates from Myanmar2017

    • Author(s)
      Nan Aye Thida Oo, Lai Lai San, Khin Saw Aye, Wah Wah Aung, Chie NAKAJIMA, Yasuhiko SUZUKI
    • Organizer
      第16回あわじしま感染症・免疫フォーラム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of genetic diversity of multi-drug resistant Mycobacterium tuberculosis Central Asian Strain isolates from Nepal and comparison with neighboring countries2017

    • Author(s)
      Yogendra Shah, Bhagwan Maharjan, Jeewan Thapa, Ajay Poudel, Hassan Mahmoud Diab, Yasuhiko Suzuki, Chie Nakajima
    • Organizer
      第16回あわじしま感染症・免疫フォーラム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular analysis of streptomycin-resistance associating genes on Mycobacterium tuberculosis isolates from Nepal2017

    • Author(s)
      Shrestha D, Maharjan B, Oo NAT, Nakajima C, Suzuki Y
    • Organizer
      The 48th Union World Conference on Lung Health
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Predominance of modern sublineage of Mycobacterium tuberculosis Beijing genotype among clinical isolates in Nepal.2017

    • Author(s)
      Poudel A, Maharjan B, Suzuki Y, Nakajima C
    • Organizer
      The 48th Union World Conference on Lung Health
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multi and extensively drug resistant tuberculosis.2017

    • Author(s)
      Suzuki Y, Nakajima C
    • Organizer
      PROGRAM OF THE SCIENTIFIC SEMINAR ON THE TOPIC OF INNOVATIVE USE OF AN ALTERNATIVE TO ANTIBIOTICS IN THE PREVENTION AND TREATMENT OF INFECTIOUS DISEASES ANIMALS
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular Epidemiological Analysis of Tuberculosis in Asia2017

    • Author(s)
      Suzuki Y, Nakajima C
    • Organizer
      2nd International Conference on Tropical Medicine
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Insight into the Beijing family multidrug-resistant tuberculosis strains from Myanmar2016

    • Author(s)
      Lai Lai San, Nan Aye Thida Oo, Khin Saw Aye, Chie NAKAJIMA, Yasuhiko SUZUKI
    • Organizer
      第一回抗酸菌研究会勉強会
    • Place of Presentation
      琉球大学50周年記念館(沖縄県那覇市)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] Detection of drug resistance-associating mutations in multidrug resistant Mycobacterium tuberculosis isolates from Myanmar2016

    • Author(s)
      Nan Aye Thida Oo, Lai Lai San, Khin Saw AYE, Wah Wah AUNG, Chie NAKAJIMA, Yasuhiko SUZUKI
    • Organizer
      第83回日本細菌学会北海道支部学術総会
    • Place of Presentation
      北海道大学歯学部講堂(札幌市)
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
  • [Presentation] High diversity of Mycobacterium tuberculosis Central Asian Strain family isolates in Nepalese patients2016

    • Author(s)
      Yogendra Shah, Bhagwan Maharjan, Ajay Poudel, Hassan Mahmoud Diab, Jeewan Thapa, Chie Nakajima, Yasuhiko Suzuki
    • Organizer
      Colorado Mycobacteria Conference 2016
    • Place of Presentation
      Colorado State University, Fort Collins, Colorado (米国)
    • Year and Date
      2016-06-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] MIRU-VNTR typing of Beijing family multidrug resistant Mycobacterium tuberculosis in Myanmar2016

    • Author(s)
      Lai Lai San, Nan Aye Thida Oo, Wah Wah Aung, Khin Saw Aye, Chie Nakajima, Yasuhiko Suzuki
    • Organizer
      Colorado Mycobacteria Conference 2016
    • Place of Presentation
      Colorado State University, Fort Collins, Colorado (米国)
    • Year and Date
      2016-06-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of MIRU-VNTR typing of MDRMTB Beijing genotype isolates in Nepal.2016

    • Author(s)
      Yogendra Shah,Jeewan Thapa,Ajay Poudel,Bhagwan Maharjan,Chie Nakajima, Yasuhiko Suzuki
    • Organizer
      第89回日本細菌学会総会
    • Place of Presentation
      大阪国際交流センター(大阪市)
    • Year and Date
      2016-03-23
    • Related Report
      2015 Research-status Report
  • [Presentation] MOLECULAR EPIDEMIOLOGY OF MULTIDRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS IN ASIAN COUNTRIES2016

    • Author(s)
      Chie Nakajima, Bhagwan Maharjan, Khin Saw Aye, Zeaur Rahim, Benjawan Phetsuksiri, Aki Tamaru, Nan Aye Thida Oo, Lai Lai San, Yogendra Shah, Janisara Rudeeaneksin, Jeewan Thapa, Ajay Poudel and Yasuhiko Suzuki
    • Organizer
      US-Japan CMSP 50th Anniversary TB, Leprosy Panel Meeting
    • Place of Presentation
      Bethesda North Marriott Hotel & Conference Center (U.S.A.)
    • Year and Date
      2016-01-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Detection of pncA gene mutations in multidrug-resistant Mycobacterium tuberculosis isolates from Myanmar2016

    • Author(s)
      Nan Aye Thida OO, Lai Lai SAN, Khin Saw AYE, Wah Wah AUNG, Chie NAKAJIMA, Yasuhiko SUZUKI
    • Organizer
      US-Japan CMSP 50th Anniversary TB, Leprosy Panel Meeting
    • Place of Presentation
      Bethesda North Marriott Hotel & Conference Center (U.S.A.)
    • Year and Date
      2016-01-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] MIRU-VNTR Typing of Beijing MDR-TB strains from Myanmar2016

    • Author(s)
      Lai Lai San, Nan Aye Thida Oo, Wah Wah Aung, Khin Saw Aye, Chie Nakajima, Yasuhiko Suzuki
    • Organizer
      US-Japan CMSP 50th Anniversary TB, Leprosy Panel Meeting
    • Place of Presentation
      Bethesda North Marriott Hotel & Conference Center (U.S.A.)
    • Year and Date
      2016-01-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genetic Diversity and Transmission Dynamics of Multidrug Resistant Tuberculosis in Nepal2016

    • Author(s)
      Bhagwan Maharjan, Yasuhiko Suzuki, Chie Nakajima, Ajay Poudel, Harald Hoffmann, Korkut Avsar, Bhabana Shrestha, Jeewan Thapa, Yogendra Shah, Rajendra Pant
    • Organizer
      US-Japan CMSP 50th Anniversary TB, Leprosy Panel Meeting
    • Place of Presentation
      Bethesda North Marriott Hotel & Conference Center (U.S.A.)
    • Year and Date
      2016-01-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular characteristics and genotypes of Mycobacterium tuberculosis isolated from an outbreak of Thailand-Myanmar border2016

    • Author(s)
      Janisara Rudeeaneksin, Benjawan Phetsuksiri, Supranee Bunchoo, Sopa Srisungngam, Wiphat Klayut, Somchai Sangkitporn, Anupong Sujariyakul, Krairerk Suthum, Nattakan Tipkrual, Yukari Fukushima3 Haruka Suzuki, Chie Nakajima, Yasuhiko Suzuki
    • Organizer
      US-Japan CMSP 50th Anniversary TB, Leprosy Panel Meeting
    • Place of Presentation
      Bethesda North Marriott Hotel & Conference Center (U.S.A.)
    • Year and Date
      2016-01-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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