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Construction of chimeric bacteria and analysis of host specificity determination mechanism of pathogenic bacteria

Research Project

Project/Area Number 18K19446
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionOsaka University

Principal Investigator

Horiguchi Yasuhiko  大阪大学, 微生物病研究所, 教授 (00183939)

Project Period (FY) 2018-06-29 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords細胞融合 / キメラ細菌 / 気管支敗血症菌 / パラ百日咳菌
Outline of Final Research Achievements

To analyze the mechanism of determining host specificity of pathogenic bacteria at the genetic level, we attempted to generate chimeric bacteria that infect non-human laboratory animals by fusing B. parapertussis, which infects only humans, and B. bronchiseptica, which infects a wide range of mammalian species. As a result, we isolated candidate strains for fused bacterial cells at a rate of about 0.01% of the number of bacteria tested. Of these strains, about 10% showed the potential for genomic hybridization. Unfortunately, however, we were unable to achieve our initial goal due to problems such as recombination occurring in a shorter genomic region than expected and the occurrence of mutant strains with spontaneous inversion of the genomic structure in parental B. bronchiseptica.

Academic Significance and Societal Importance of the Research Achievements

細胞の融合技術は40年以上前に隆盛し、微生物では品種改良の目的で乳酸菌、糸状菌、酵母などで利用されたが、特定の遺伝子を標的にできる、より精細な遺伝子操作技術が発展した現在ではほとんど利用されない。異なる種の真正細菌の細胞融合に関する研究はさらに少なく、種々の方法論が確立される前に研究が衰退してしまったため、現在の科学の動向や水準からみて参考となる知見はほとんどない。本研究課題では所期の目的は達成できなかったが、細胞融合の基準プロトコールと融合候補細菌の遺伝子解析の結果を示すことができた。その成果は、キメラ細菌の作製技術の再理解のための最新の知見を提供すると考えている。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Melanin Produced by <i>Bordetella parapertussis</i> Confers a Survival Advantage to the Bacterium during Host Infection2021

    • Author(s)
      Hiramatsu Yukihiro、Nishida Takashi、Nugraha Dendi Krisna、Sugihara Fuminori、Horiguchi Yasuhiko
    • Journal Title

      mSphere

      Volume: 6 Issue: 5

    • DOI

      10.1128/msphere.00819-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis2020

    • Author(s)
      Tsukamoto Kentaro、Shinzawa Naoaki、Kawai Akito、Suzuki Masahiro、Kidoya Hiroyasu、Takakura Nobuyuki、Yamaguchi Hisateru、Kameyama Toshiki、Inagaki Hidehito、Kurahashi Hiroki、Horiguchi Yasuhiko、Doi Yohei
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 3571-3571

    • DOI

      10.1038/s41467-020-17391-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the minimum region of Bordetella pertussis Vag8 required for interaction with C1 inhibitor2020

    • Author(s)
      Onoda Naoki、Hiramatsu Yukihiro、Teruya Shihono、Suzuki Koichiro、Horiguchi Yasuhiko
    • Journal Title

      Microbiology and Immunology

      Volume: 64 Issue: 8 Pages: 570-573

    • DOI

      10.1111/1348-0421.12799

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of small RNAs of Bordetella pertussis colonizing murine tracheas2020

    • Author(s)
      Hiramatsu Yukihiro、Suzuki Koichiro、Motooka Daisuke、Nakamura Shota、Horiguchi Yasuhiko
    • Journal Title

      Microbiology and Immunology

      Volume: - Issue: 6 Pages: 469-475

    • DOI

      10.1111/1348-0421.12791

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bordetella Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses CaV3.1 as the Cell Surface Receptor.2020

    • Author(s)
      Teruya S, Hiramatsu Y, Nakamura K, Fukui-Miyazaki A, Tsukamoto K, Shinoda N, Motooka D, Nakamura S, Ishigaki K, Shinzawa N, Nishida T, Sugihara F, Maeda Y, Horiguchi Y.
    • Journal Title

      mBio

      Volume: 11 Issue: 2 Pages: 03146-19

    • DOI

      10.1128/mbio.03146-19

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bordet‐Gengou agar medium supplemented with albumin‐containing biologics for cultivation of bordetellae2019

    • Author(s)
      Hiramatsu Yukihiro、Osada‐Oka Mayuko、Horiguchi Yasuhiko
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 12 Pages: 513-516

    • DOI

      10.1111/1348-0421.12742

    • NAID

      40022103554

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] BspR/BtrA, an Anti-σ Factor, Regulates the Ability of Bordetella bronchiseptica To Cause Cough in Rats2019

    • Author(s)
      Nakamura Keiji、Shinoda Noriko、Hiramatsu Yukihiro、Ohnishi Shinya、Kamitani Shigeki、Ogura Yoshitoshi、Hayashi Tetsuya、Horiguchi Yasuhiko
    • Journal Title

      mSphere

      Volume: 4 Issue: 2

    • DOI

      10.1128/msphere.00093-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Bordetella bronchiseptica utilizes Acanthamoeba castellanii2022

    • Author(s)
      Dendi Krisna Nugraha、山口 博之、堀口 安彦
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Bordetella parapertussis produces melanin involvoed in the bacterial survival during host infection2022

    • Author(s)
      平松 征洋、西田 隆司、Dendi Krisna Nugraha、堀口 安彦
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ボルデテラの毒素2022

    • Author(s)
      堀口 安彦
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 感染動物実験から見えた百日咳における脳症と咳発作2021

    • Author(s)
      堀口 安彦
    • Organizer
      第68回日本実験動物学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マウス咳発症モデルを用いた百日咳の咳発症メカニズムの解析2021

    • Author(s)
      平松 征洋、鈴木 孝一朗、西田 隆司、堀口 安彦
    • Organizer
      第15回細菌学若手コロッセウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 百日咳の咳発作はリポオリゴサッカライド、Vag8、百日咳毒素の協調作用によって起こる2021

    • Author(s)
      平松 征洋、鈴木 孝一朗、西田 隆司、堀口 安彦
    • Organizer
      第67回トキシンシンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Bordetella bronchiseptica utilizes Acanthamoeba castellanii as a temporal niche2021

    • Author(s)
      Dendi Krisna Nugraha、Hiroyuki Yamaguchi、Yasuhiko Horiguchi
    • Organizer
      第19回あわじ感染と免疫国際フォーラム
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bordetella bronchiseptica utilizes Acanthamoeba castellanii as a temporal niche2021

    • Author(s)
      Dendi Krisna Nugraha、山口 博之、堀口 安彦
    • Organizer
      第74回日本細菌学会関西支部総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] パラ百日咳菌の産生する褐色色素メラニンの同定と機能解析2021

    • Author(s)
      平松 征洋、西田 隆司、Dendi Krisna Nugraha、堀口 安彦
    • Organizer
      第74回日本細菌学会関西支部総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The mechanism of pertussis cough revealed by the mouse-coughing model2021

    • Author(s)
      平松 征洋、鈴木 孝一朗、西田 隆司、堀口 安彦
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 宿主感染時に高発現する百日咳菌small RNAの機能解析2020

    • Author(s)
      平松 征洋、鈴木 孝一朗、堀口 安彦
    • Organizer
      第73回日本細菌学会関西支部総会
    • Related Report
      2020 Research-status Report
  • [Presentation] マウスモデルから見た百日咳における咳発作発症機構2020

    • Author(s)
      平松 征洋、鈴木 孝一朗、西田 隆司、堀口 安彦
    • Organizer
      第73回日本細菌学会関西支部総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Bordetella bronchiseptica utilizes Acanthamoeba catellanii as a temporal niche2020

    • Author(s)
      Dendi Krisna Nugraha、山口 博之、堀口 安彦
    • Organizer
      第73回日本細菌学会関西支部総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 新規発光システムを用いた気管支敗血症菌感染のin vivoイメージング手法の構築2020

    • Author(s)
      玉木 優生、西田 隆司、平松 征洋、堀口 安彦
    • Organizer
      第73回日本細菌学会関西支部総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Modification of Bordet-Gengou agar medium for cultivation of bordetellae2020

    • Author(s)
      平松征洋、岡真優子、堀口安彦
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Presentation] Bordetella bronchiseptica utilizes Acanthamoeba castellanii as a temporal niche2020

    • Author(s)
      Dendi Krisna Nugraha、山口博之,堀口安彦
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of Bordetella dermonecrotic toxin receptor2019

    • Author(s)
      平松征洋、照屋志帆乃、中村佳司、福井理、塚本健太郎、堀口安彦
    • Organizer
      第18回あわじ感染と免疫国際フォーラム
    • Related Report
      2019 Research-status Report
  • [Presentation] ボルデテラ壊死毒(DNT)の受容体同定を通じた百日咳病態の解析2019

    • Author(s)
      照屋志帆乃、平松征洋、篠田典子、塚本健太郎、中村佳司、石垣圭祐、堀口安彦
    • Organizer
      第66回トキシンシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of Bordetella dermonecrotic toxin receptor2019

    • Author(s)
      Shihono Teruya, Yukihiro Hiramatsu, Noriko Shinoda, Kentao Tsukamoto, Keiji Nakamura, Aya Fukui-Miyazaki, Keisuke Ishigaki, Yasuhiko Horiguchi
    • Organizer
      ETOX19
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 百日咳に対する鎮咳薬および百日咳に対する鎮咳薬のスクリーニング法2019

    • Inventor(s)
      堀口安彦、平松征洋
    • Industrial Property Rights Holder
      堀口安彦、平松征洋
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2018-07-25   Modified: 2023-01-30  

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