Identification of host genes required for the protection against a lethal infection of Francisella tularensis

• Project/Area Number: 16K09955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: UDA AKIHIKO 国立感染症研究所, 獣医科学部, 主任研究官 (80392322)
• Research Collaborator: Tian Deyu ; Azaki Mika
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 野兎病菌 / 野兎病 / ワクチン / 感染防御 / 免疫反応 / LCN2 / GBP / Iba1陽性マクロファージ / 免疫 / Francisella / 人獣共通感染症 / 遺伝子 / 感染症 / マイクロアレイ

Outline of Final Research Achievements

Tularemia is a severe and sometimes fatal zoonotic disease caused by the Gram-negative intracellular bacterium Francisella tularensis. F. tularensis SCHU P9 derived Δftt_0965c strain lacking the ftt_0965c (sulfite exporter) gene conferred stable and good protection in a mouse lethal model. In this study, the immune responses of mice vaccinated with and without Δftt_0965c strain after the challenge of virulent F. tularensis SCHU P9 were compared by microarray and immunohistochemical analysis. These finding suggested that lipocalin 2 and GBP produced by Iba1-positive macrophages would be indispensable for the protection against lethal infection by F. tularensis.

Academic Significance and Societal Importance of the Research Achievements

これまでに、野兎病菌の病原性に関する研究は、野兎病菌が保持する遺伝子に注目されてきた。本研究は、野兎病菌の高い感染性や病原性を抑制可能な感染宿主遺伝子を同定することにより、弱毒化機序が明確で安全な野兎病菌ワクチンを開発するための基礎を築いた。

Research Products

• [Journal Article] Evaluation of Francisella tularensis ΔpdpC as a candidate live attenuated vaccine against respiratory challenge by a virulent SCHU P9 strain of Francisella tularensis in a C57BL/6J mouse model (2018)
  • Author(s): Tian Deyu、Uda Akihiko、Park Eun-sil、Hotta Akitoyo、Fujita Osamu、Yamada Akio、Hirayama Kazuhiro、Hotta Kozue、Koyama Yuuki、Azaki Mika、Morikawa Shigeru
  • Journal Title: Microbiology and Immunology Volume: 62 Issue: 1 Pages: 24-33
  • DOI: 10.1111/1348-0421.12555
  • NAID: 40021443639
• [Journal Article] Pullulanase Is Necessary for the Efficient Intracellular Growth of Francisella tularensis (2016)
  • Author(s): Uda A, Sharma N, Takimoto K, Deyu T,, Koyama Y,, Park ES, Fujita O, Hotta A, Morikawa S
  • Journal Title: PLoS One Volume: 11 Issue: 7 Pages: e0159740-e0159740
  • DOI: 10.1371/journal.pone.0159740
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 野兎病菌の不活化条件に関する調査 (2018)
  • Author(s): 阿崎美佳, 宇田晶彦, 田徳雨, 堀田明豊, 森川茂, 森川茂
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] 野兎病菌の安定性と不活化に関する包括的な検討 (2018)
  • Author(s): 宇田晶彦
  • Organizer: 第18回日本バイオセーフティ学会総会・学術集会
• [Presentation] Evaluation of a Novel Francisella Tularensis Live Attenuated Vaccine Candidate in C57bl/6j Mouse Model. (2017)
  • Author(s): Deyu T, Uda A, Park ES, Hotta A, Fujita O, Yamada A, Hirayama K, Hotta K, Koyama Y, and Morikawa S
  • Organizer: XVth International Congress of Bacteriology and Applied Microbiology.
  • Int'l Joint Research
• [Presentation] Update on epidemiology and diagnostic approaches of Francisella tularensis (2017)
  • Author(s): Uda A
  • Organizer: Workshop The development of the rapid molecular test kits for detecting pathogens of importance for human and animal health
  • Int'l Joint Research / Invited
• [Presentation] 野兎病菌の表皮上からの感染性の検証 (2017)
  • Author(s): 堀田明豊, 朴Ensil, 藤田修, 田徳雨, 宇田晶彦, 森川茂
  • Organizer: 160回日本獣医学会学術集会
• [Presentation] 野兎病菌強毒株および弱毒株感染マクロファージの免疫応答に関する検討 (2017)
  • Author(s): 阿崎美佳, 宇田晶彦, 中里勝芳, 田徳雨, 堀田明豊, 藤田修, 森川茂
  • Organizer: 160回日本獣医学会学術集会
• [Presentation] 野兎病菌プルラナーゼ遺伝子の病原性に関する検討 (2016)
  • Author(s): 宇田晶彦、Neekun Sharma、滝本一広、田徳雨、古山裕樹、朴ウンシル、 藤田修、堀田明豊、森川茂
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 神奈川