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Role of the bactericidal lectin RegIIIbeta in Salmonella gut infection

Research Project

Project/Area Number 16K08783
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionKitasato University

Principal Investigator

Miki Tsuyoshi  北里大学, 薬学部, 講師 (40398582)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords抗菌レクチン / サルモネラ / 腸炎 / バクテロイデス属細菌 / ビタミンB6 / RegIIIbeta / サルモネラ腸炎 / Bacteroides属細菌 / ビタミン / 病原体排除 / 細菌 / 感染症 / 腸内細菌
Outline of Final Research Achievements

The bactericidal lectin RegIIIbeta is believed to be an immune effector, which protects from gut infection with bacterial pathogens. However, it was poorly understood how RegIIIbeta involves gut homeostasis by its bactericidal activity. In this study, we studied the role of RegIIIbeta in Salmonella gut infection by using the streptomycin mouse model for Salmonella diarrhea. Inducible expression of RegIIIbeta prolonged the Salmonella gut colonization and the enteropathy. RegIIIbeta also impacted the gut microbiota composition, which is characterized by suppression of Bacteroides spp. in the gut lumen. This dysbiosis can alter the colonic metabolism, resulting in reduced luminal vitamin B6 levels. Supplementation with Bacteroides app. or vitamin B6 accelerated Salmonella clearance from the gut and remission of enteropathy. Collectively, these findings suggest that RegIIIbeta does not act as a protective effector, rather unexpectedly helps Salmonella gut infection.

Academic Significance and Societal Importance of the Research Achievements

本研究の研究結果はRegIIIbeta、バクテロイデス属細菌およびビタミンB6がサルモネラ腸炎の新たな治療ターゲットになる可能性を示した。近年、さまざまな疾患において、ディスバイオーシスが病態の増悪に関与することが報告されている。Clostridium difficile感染性腸炎に対する便細菌叢移植療法に代表されるように、腸内細菌叢および腸内環境の是正をめざしたアプローチは新たな治療法として、期待される。我々の研究知見は、ビタミンの産生能などを考慮した便細菌移植やビタミン投与の併用が、新たな治療法になる可能性を示唆する。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(7 results)

All 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) Book (1 results)

  • [Journal Article] Tat-exported peptidoglycan amidase-dependent cell division contributes to Salmonella Typhimurium fitness in the inflamed gut2018

    • Author(s)
      Fujimoto Mayuka、Goto Ryosuke、Hirota Riku、Ito Masahiro、Haneda Takeshi、Okada Nobuhiko、Miki Tsuyoshi
    • Journal Title

      PLOS Pathogens

      Volume: 14

    • DOI

      10.1371/journal.ppat.1007391

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Salmonella Typhimurium CpxRA two-component system contributes to gut colonization in Salmonella-induced colitis2018

    • Author(s)
      Mayuka Fujimoto, Ryosuke Goto, Takeshi Haneda, Nobuhiko Okada, and Tsuyoshi Miki
    • Journal Title

      Infection and Immunity

      Volume: 00 Pages: 0000-0000

    • DOI

      10.1128/iai.00280-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inflammatory bactericidal lectin RegIIIβ: Friend or foe for the host?2017

    • Author(s)
      Miki Tsuyoshi、Okada Nobuhiko、Hardt Wolf-Dietrich
    • Journal Title

      Gut Microbes

      Volume: 0 Pages: 1-9

    • DOI

      10.1080/19490976.2017.1387344

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization2017

    • Author(s)
      Goto Ryosuke、Miki Tsuyoshi、Nakamura Nao、Fujimoto Mayuka、Okada Nobuhiko
    • Journal Title

      PLoS One

      Volume: 12

    • DOI

      10.1371/journal.pone.0190095

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The bactericidal lectin RegIIIbeta prolongs gut colonization and enteropathy in the streptomycin mouse model for Salmonella diarrhea2017

    • Author(s)
      Tsuyoshi Miki, Ryosuke Goto, Mayuka Fujimoto, Nobuhiko Okada, and Wolf-Dietrich Hardt
    • Journal Title

      Cell Host & Microbe

      Volume: 21 Pages: 195-207

    • DOI

      10.1016/j.chom.2016.12.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] RegIIIbeta lectin prolongs the gut colonization and enteropathy inflicted with Salmonella Typhimurium2017

    • Author(s)
      Tsuyoshi Miki and Nobuhiko Okada
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台国際センター展示棟
    • Year and Date
      2017-03-18
    • Related Report
      2016 Research-status Report
  • [Book] 臨床免疫・アレルギー科2017

    • Author(s)
      三木剛志
    • Total Pages
      454
    • Publisher
      科学評論社
    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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