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Screening of in vivo essential factor inhibiters for multi-drug resistant bacteria

Research Project

Project/Area Number 17K15688
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bacteriology (including mycology)
Research InstitutionSapporo Medical University

Principal Investigator

Sato Toyotaka  札幌医科大学, 医学部, 助教 (30756474)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords細菌 / 薬剤耐性菌 / 生体内菌発育必須因子 / vivoEF / 多剤耐性 / 感染部位特異的治療 / 敗血症 / 血流感染症 / 多剤耐性菌 / 抗菌薬 / 化合物スクリーニング / 感染症
Outline of Final Research Achievements

In this study, we focused on bacterial factors that are essential for their bacterial growth and survival (vivoEF) in vivo(infected sites such as tissues and blood), but not for in vitro, from a view of emergence and spread of multidrug-resistant bacteria that is considered to be a problem in the future. We screened and identified vivoEF inhibitors. We also identified their targets in bacteria, and evaluated vivoEF effects using infectious models in mouse. As a result, a plurality of compounds showing antibacterial activity only in blood were identified, and it was clarified that the compounds suppress the production of bacterial capsule. From the above, we obtained scientific findings on new treatments for bacterial bloodstream infections such as sepsis in this study.

Academic Significance and Societal Importance of the Research Achievements

敗血症といった細菌性血流感染症による死亡率は増加の一途をたどっており、多剤耐性菌はその治療を一層困難にしている。よって本研究で明らかにした、『生体内菌発育必須因子(vivoEF) 』とその阻害剤の同定から得た科学的知見は、多剤耐性化や新たな耐性菌を生み出さない新たな感染症治療戦略の確立に寄与する重要な意義を持つと考えられる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Contribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in mcr-Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131-H30Rx and Non-x2018

    • Author(s)
      Sato Toyotaka、Shiraishi Tsukasa、Hiyama Yoshiki、Honda Hiroyuki、Shinagawa Masaaki、Usui Masaru、Kuronuma Koji、Masumori Naoya、Takahashi Satoshi、Tamura Yutaka、Yokota Shin-ichi
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 62 Issue: 9

    • DOI

      10.1128/aac.00864-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiclonal Expansion and High Prevalence of β-Lactamase-Negative Haemophilus influenzae with High-Level Ampicillin Resistance in Japan and Susceptibility to Quinolones2018

    • Author(s)
      Honda Hiroyuki、Sato Toyotaka、Shinagawa Masaaki、Fukushima Yukari、Nakajima Chie、Suzuki Yasuhiko、Shiraishi Tsukasa、Kuronuma Koji、Takahashi Satoshi、Takahashi Hiroki、Yokota Shin-ichi
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 62 Issue: 9

    • DOI

      10.1128/aac.00851-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole genome analysis of a multidrug-resistant Streptococcus pneumoniae isolate from a patient with invasive pneumococcal infection developing disseminated intravascular coagulation2018

    • Author(s)
      Ohkoshi Yasuo、Sato Toyotaka、Wada Takayuki、Fukushima Yukari、Murabayashi Hiromi、Takakuwa Yasunari、Nishiyama Kaoru、Honda Hiroyuki、Shiraishi Tsukasa、Kuronuma Koji、Takahashi Hiroki、Nakajima Chie、Suzuki Yasuhiko、Yokota Shin-ichi
    • Journal Title

      J Infect Chemother

      Volume: 印刷中 Issue: 8 Pages: 674-681

    • DOI

      10.1016/j.jiac.2018.01.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation of a mcr-1-harbouring Escherichia coli isolate from a human clinical setting in Sapporo, Japan2018

    • Author(s)
      Sato T, Fukuda A, Usui M, Shinagawa M, Shiraishi T, Tamura Y, Takahashi S, Yokota SI
    • Journal Title

      J Glob Antimicrob Resist

      Volume: 13 Pages: 20-21

    • DOI

      10.1016/j.jgar.2018.02.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Release of high amounts of lipopolysaccharides from Pseudomonas aeruginosa cells reduces their susceptibility to colistin2018

    • Author(s)
      Yokota SI, Hakamada H, Yamamoto S, Sato T, Shiraishi T, Shinagawa M, Takahashi S
    • Journal Title

      Int J Antimicrob Agents

      Volume: 印刷中 Issue: 6 Pages: 888-896

    • DOI

      10.1016/j.ijantimicag.2018.02.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of consistency in quantification of gene copy number by real-time reverse transcription quantitative polymerase chain reaction and virus titer by plaque-forming assay for human respiratory syncytial virus.2018

    • Author(s)
      Yamamoto K, Ogasawara N, Yamamoto S, Takano K, Shiraishi T, Sato T, Tsutsumi H, Himi T, Yokota SI.
    • Journal Title

      Microbiol Immunol.

      Volume: 62 Issue: 2 Pages: 90-98

    • DOI

      10.1111/1348-0421.12563

    • NAID

      40021481337

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] High prevalence of mcr-1, mcr-3 and mcr-5 in Escherichia coli derived from diseased pigs in Japan2018

    • Author(s)
      Fukuda A, Sato T, Shinagawa M, Takahashi S, Asai T, Yokota SI, Usui M, Tamura Y
    • Journal Title

      Int J Antimicrob Agents

      Volume: 51 Issue: 1 Pages: 163-164

    • DOI

      10.1016/j.ijantimicag.2017.11.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tigecycline Susceptibility of Klebsiella pneumoniae Complex and Escherichia coli Isolates from Companion Animals: The Prevalence of Tigecycline-Nonsusceptible K. pneumoniae Complex, Including Internationally Expanding Human Pathogenic Lineages2017

    • Author(s)
      Sato T, Harada K, Usui M, Tsuyuki Y, Shiraishi T, Tamura Y, Yokota SI
    • Journal Title

      Microb Drug Resist

      Volume: 12 Issue: 6 Pages: 860-867

    • DOI

      10.1089/mdr.2017.0184

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Complete Genome Sequence of Multidrug-Resistant Streptococcus pneumoniae Serotype 19F Isolated from an Invasive Infection in Sapporo, Japan2017

    • Author(s)
      Sato T, Ohkoshi Y, Wada T, Fukushima Y, Murabayashi H, Takakuwa Y, Nishiyama K, Shiraishi T, Nakajima C, Suzuki Y, Yokota SI
    • Journal Title

      Genome Announc

      Volume: 5 Issue: 44

    • DOI

      10.1128/genomea.01239-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel antimicrobial activities of a peptide derived from a Japanese soybean fermented food, Natto, against Streptococcus pneumoniae and Bacillus subtilis group strains.2017

    • Author(s)
      Manabu Kitagawa, Tsukasa Shiraishi, Soh Yamamoto, Ryosuke Kutomi, Yasuo Ohkoshi, Toyotaka Sato, Hideki Wakui, Hideaki Itoh, Atsushi Miyamoto, Shin-ichi Yokota.
    • Journal Title

      AMB Express

      Volume: 7 Issue: 1 Pages: 127-127

    • DOI

      10.1186/s13568-017-0430-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mycoplasma bovis isolates from dairy calves in Japan have less susceptibility than a reference strain to all approved macrolides associated with a point mutation (G748A) combined with multiple species-specific nucleotide alterations in 23S rRNA2017

    • Author(s)
      Sato T, Higuchi H, Yokota SI, Tamura Y
    • Journal Title

      Microbiol Immunol

      Volume: 61 Issue: 6 Pages: 215-224

    • DOI

      10.1111/1348-0421.12490

    • NAID

      40021227543

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47phox.2017

    • Author(s)
      Bharatwaj Sowrirajan, Yoshiro Saito, Deepak Poudyal, Qian Chen, Hongyan Sui, Suk See DeRavin, Hiromi Imamichi, Toyotaka Sato, Douglas B. Kuhns, Noriko Noguchi, Harry L. Malech, H. Clifford Lane and Tomozumi Imamichi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 43441-43441

    • DOI

      10.1038/srep43441

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Molecular epidemiological analysis of antimicrobial drug-resistant Streptococcus penumoniae and Haemophilus influenzae isolated in Sapporo, in Japan2019

    • Author(s)
      T. Sato
    • Organizer
      U.S.-Japan Cooperative Medical Sciences Program (USJCMSP), 21st Acute Respiratory Infections (ARI) Panel Meeting
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] In vivo generation of extensively drug-resistant Klebsiella pneumoniae via a disrupting mutation in the DNA repair enzyme MutS2018

    • Author(s)
      T. Sato, M. Shinagawa, S. Nishijima, Y. Fukushima, C. Nakajima, H. Honda, T. Shiraishi, K. Kuronuma, H. Takahashi, Y. Suzuki, S. Takahashi, Y. SI. Yokota
    • Organizer
      ASM Microbe 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genetic analysis of high-level β-lactamase-negative ampicillin-resistant strains and in vitro-selected fluoroquinolone-resistant mutants of Haemophilus influenzae2018

    • Author(s)
      Honda H, Sato T, Shinagawa M, Fukushima Y, Nakajima C, Suzuki Y, Shiraishi T, Kuronuma K, Takahashi S, Takahashi H, Yokota SI
    • Organizer
      ASM Microbe 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大腸菌臨床分離株におけるepidemic clone, ST131のコリスチン及びチゲサイクリン耐性2018

    • Author(s)
      Toyotaka Sato, Masaru Usui, Masaaki Shinagawa, Akira Fukuda, Hiroyuki Honda, Tsukasa Shiraishi, Hiroki Takahashi, Yutaka Tamura, Satoshi Takahashi, Shin-ichi Yokota
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 入院治療中にアミカシン耐性を獲得した多剤耐性Klebsiella pneumoniaeの全ゲノム解析2018

    • Author(s)
      佐藤 豊孝、品川 雅明、高橋 聡、横田 伸一
    • Organizer
      第92回日本感染症学会総会・学術講演会 第66回日本化学療法学会学術講演会合同学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 医療で重要なペット由来薬剤耐性大腸菌2018

    • Author(s)
      佐藤 豊孝
    • Organizer
      第8回 日本医師会・日本獣医師会による連携シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Molecular epidemiological analysis of antimicrobial resistant bacteria isolated from animals and human2018

    • Author(s)
      T. Sato
    • Organizer
      The 7th bacteriology Special Seminar.
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 大腸菌臨床分離株における epidemic clone ST131 のコリスチンお よびチゲサイクリン耐性2018

    • Author(s)
      佐藤 豊孝,臼井 優,品川 雅明,福田 昭,本田 宏幸,白 石 宗,田村 豊,高橋 聡,横田 伸一
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] β-lactamase-negative ampicillin-resistant Haemophilus influenzae 臨床分離株の遺伝学的特徴2018

    • Author(s)
      本田 宏幸,佐藤 豊孝,高橋 弘毅,横田 伸一
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Tigecycline non-susceptibility occurs exclusively in fluoroquinolone-resistant Escherichia coli clinical isolates, including the major multidrug-resistant lineages O25b:H4-ST131-H30R and O1-ST6482017

    • Author(s)
      T. Sato, Y. Suzuki, T. Shiraishi, H. Honda, M. Shinagawa, S. Yamamoto, N. Ogasawara, S. Takahashi, Y. Tamura, SI. Yokota
    • Organizer
      ASM Microbe 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] コリスチン耐性大腸菌臨床分離株の耐性機構の解析2017

    • Author(s)
      佐藤 豊孝、福田 昭、白石 宗、品川 雅明、 山本 聡、小笠原 徳子、臼井 優、高橋 聡、田村 豊、横田 伸一
    • Organizer
      第11回細菌学若手コロッセウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 基礎から見た臨床現場の耐性菌2017

    • Author(s)
      佐藤 豊孝
    • Organizer
      第2回北海道微生物検査研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] 化学療法の領域(抗菌薬多剤耐性におけるefflux pumpの役割を見直す)2017

    • Author(s)
      横田伸一、佐藤豊孝
    • Total Pages
      6
    • Publisher
      医薬ジャーナル社
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 抗菌薬のスクリーニング法2017

    • Inventor(s)
      佐藤豊孝、横田伸一
    • Industrial Property Rights Holder
      佐藤豊孝、横田伸一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-01-27  

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