Updated on 2026/01/21

写真a

 
Ryo Kinoshita-Daitoku
 
Organization
Graduate School of Medicine Program in Integrated Medicine Microbiology and Immunology Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Assistant Professor

Degree 1

  1. 博士 (医学) ( 2019.3   東京大学 ) 

Research History 2

  1. Osaka University   Assistant Professor

    2020.6 - 2021.6

  2. Osaka University   Researcher

    2019.4 - 2020.5

 

Papers 11

  1. A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment. Reviewed Open Access

    Ryo Kinoshita-Daitoku, Kotaro Kiga, Masatoshi Miyakoshi, Ryota Otsubo, Yoshitoshi Ogura, Takahito Sanada, Zhu Bo, Tuan Vo Phuoc, Tokuju Okano, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Sayaka Hirukawa, Mototsugu Tanaka, Arpana Sood, Phawinee Subsomwong, Hiroshi Ashida, Tran Thanh Binh, Lam Tung Nguyen, Khien Vu Van, Dang Quy Dung Ho, Kenta Nakai, Toshihiko Suzuki, Yoshio Yamaoka, Tetsuya Hayashi, Hitomi Mimuro

    Nature communications     2021.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: https://doi.org/10.1038/s41467-021-22317-7

    Open Access

  2. Development of two methods for detecting<i> Streptococcus</i><i> mitis/oralis-related</i> species with meropenem-non-susceptibility

    Kuri, K; Kinoshita-Daitoku, R; Arakawa, Y; Shibayama, K; Kimura, K

    JOURNAL OF INFECTION AND CHEMOTHERAPY   Vol. 31 ( 12 ) page: 102846   2025.12

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    Language:English   Publisher:Journal of Infection and Chemotherapy  

    Several studies have reported clinical isolates of Streptococcus mitis, Streptococcus oralis, and their related species (S. mitis/oralis group) with reduced carbapenem susceptibility. However, to date, no simple and accurate methods of detecting S. mitis/oralis group isolates with reduced carbapenem susceptibility have been reported. The meropenem ETEST misinterpreted 3 of 25 (12 %) meropenem-non-susceptible S. mitis/oralis group isolates as susceptible to meropenem. Therefore, we screened 38 disks containing 38 different β-lactams to detect S. mitis/oralis group strains with reduced carbapenem susceptibility using the disk-diffusion method. Additionally, using the agar dilution method to determine susceptibility, we identified the optimal antibiotic concentrations in agar medium to enable selective culture of meropenem-non-susceptible S. mitis/oralis group by culturing 25 meropenem-non-susceptible (meropenem minimum inhibitory concentration [MIC] >0.5 μg/mL) and 24 meropenem-susceptible (meropenem MIC ≤0.5 μg/mL) S. mitis/oralis group isolates on agar containing different concentrations of six β-lactams. Meropenem-susceptible and non-susceptible S. mitis/oralis group isolates were successfully differentiated using oxacillin- and cefoxitin-containing disks. Moreover, cefdinir-, flomoxef-, meropenem-, and doripenem-containing disks showed clear differences in the growth inhibitory zone diameter between the meropenem-susceptible and meropenem-non-susceptible S. mitis/oralis group isolates. Media containing 2 μg/mL oxacillin, 4–16 μg/mL cefoxitin, 2 μg/mL cefdinir, 2–4 μg/mL flomoxef, 0.06–0.25 μg/mL meropenem, and 0.06–0.12 μg/mL doripenem allowed selective culture of meropenem-non-susceptible S. mitis/oralis group strains. The disk-diffusion method using six β-lactam-containing disks and selective culture agar medium are the first-reported simple and accurate methods of detecting meropenem-non-susceptible S. mitis/oralis group suitable for use in clinical microbiology laboratories.

    DOI: 10.1016/j.jiac.2025.102846

    Web of Science

    Scopus

    PubMed

  3. Development of a nonreplicative phage-based DNA delivery system and its application to antimicrobial therapies

    Kiga, K; Sato'o, Y; Tan, XE; Miyanaga, K; Nguyen, HM; Li, FY; Azam, AH; Veeranarayanan, S; Watanabe, S; Aiba, Y; Sasahara, T; Thitiananpakorn, K; Kawaguchi, T; Nishikawa, Y; Kinoshita-Daitoku, R; Ojima, S; Kondo, K; Nakamura, T; Tamura, A; Yamashita, W; Watashi, K; Takahashi, Y; Cui, LZ

    PNAS NEXUS   Vol. 4 ( 6 ) page: pgaf176   2025.6

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    Language:English   Publisher:Pnas Nexus  

    Phage therapy has emerged as a promising alternative to conventional antimicrobial therapy for antimicrobial-resistant bacterial infections, but concerns about uncontrolled phage proliferation have limited its use. To address this issue, we established a nonproliferative phage-based DNA delivery system, called bacteria-targeting capsid particle (B-CAP), for the development of antimicrobial agents which effectively prevented phage spread while maintaining bactericidal activity. B-CAP is principally a T7 phage capsids packaged with a partial T7 phage genome, giving it the allowance to accommodate large foreign DNA up to 18 kb in length. We confirmed the efficacy of B-CAP in targeting and injecting its genome into bacteria, analogous to the wild-type phage. To demonstrate proof-of-concept and potential for developing an antimicrobial agent, we loaded colicin E1 operon onto the B-CAP system, resulting in the construction of B-CAP_ColE1, an antimicrobial agent capable of boosting colicin E1-based bacterial killing against Escherichia coli. Although no therapeutic effect was observed for B-CAP, B-CAP_ColE1 exhibited strong bactericidal activity against carbapenem-resistant E. coli both in vitro and in vivo, and significantly improved the survival of mice in an infection mouse model experiment. Finally, B-CAP_ColE1 is biologically contained or inert, reducing potential biological hazards during therapeutic use. Our results demonstrate that the B-CAP system offers a new strategy for developing nonreplicative phage-based antimicrobial agents against bacterial infections.

    DOI: 10.1093/pnasnexus/pgaf176

    Web of Science

    Scopus

    PubMed

  4. A nationwide survey of antimicrobial resistance of <i>Escherichia coli</i> isolated from broiler chickens in Malawi Reviewed

    鈴木 仁人, 木下 遼, 柴山 恵吾

    JAC-Antimicrobial Resistance   Vol. 6 ( 6 ) page: dlae200   2024

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    Language:English   Publisher:Jac Antimicrobial Resistance  

    Background: Antimicrobial resistance is a global health challenge with profound implications across sectors. Livestock, a significant field at the One Health interface, lacks sufficient information, particularly in low-resource settings such as Malawi. Objectives: We determined the antimicrobial resistance rates of Escherichia coli isolated from broiler chickens in Malawi and explored the relationship between resistance genes across sectors using genomic analysis. Methods: In 2023, we isolated 115 E. coli strains from 116 faecal and caecal samples from broiler chickens across Malawi. Antimicrobial susceptibility tests were performed using agar dilution method according to the Clinical Laboratory Standard Institute guidelines. Whole-genome sequencing was performed using Illumina sequencing. Results: Notably, 50 isolates (44%) were resistant to cefotaxime. We detected ESBL bla<inf>CTX-M</inf> genes (bla<inf>CTX-M-55</inf>, bla<inf>CTX-M-14</inf>, bla<inf>CTX-M-65</inf>, bla<inf>CTX-M-27</inf>, bla<inf>CTX-M-15</inf>, bla<inf>CTX-M-1</inf>, and bla<inf>CTX-M-3</inf>) in 48 cefotaxime-resistant isolates, which exhibited higher resistance rates to levofloxacin than non-ESBL-encoding isolates (29/48; 60% versus 20/67; 30%). All isolates were susceptible to colistin and carbapenems. High resistance rates were observed for tetracycline and co-trimoxazole commonly used in broiler chickens (90% and 70%, respectively). Sequence type 206 and phylogroup A were predominant (14% and 65%, respectively). In the genetic context of bla<inf>CTX-M</inf> genes, whole-genome alignment of the ESBL-producing isolates with reference plasmids from E. coli of various origins indicated significant similarity. Conclusions: Antimicrobial resistance is highly prevalent among E. coli from broiler chickens in Malawi. Genomic analysis suggests potential transmission pathways for ESBL genes across sectors, necessitating further studies from One Health perspective.

    DOI: 10.1093/jacamr/dlae200

    Web of Science

    Scopus

    PubMed

    CiNii Research

  5. Effect of low oxygen concentration on activation of inflammation by Helicobacter pylori. Reviewed

    Abass A, Okano T, Boonyaleka K, Kinoshita-Daitoku R, Yamaoka S, Ashida H, Suzuki T.

    Biochem Biophys Res Commun.     2021.5

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  6. Group A Streptococcus establishes pharynx infection by degrading the deoxyribonucleic acid of neutrophil extracellular traps Reviewed Open Access

    Mototsugu Tanaka, Ryo Kinoshita-Daitoku, Kotaro Kiga, Takahito Sanada, Bo Zhu, Tokuju Okano, Chihiro Aikawa, Tamako Iida, Yoshitoshi Ogura, Tetsuya Hayashi, Koshu Okubo, Miho Kurosawa, Junichi Hirahashi, Toshihiko Suzuki, Ichiro Nakagawa, Masaomi Nangaku, Hitomi Mimuro

    Scientific Reports     2020.12

  7. Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment Reviewed

    Ryo Kinoshita-Daitoku, Kotaro Kiga, Takahito Sanada, Yoshitoshi Ogura, Zhu Bo, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Mototsugu Tanaka, Arpana Sood, Toshihiko Suzuki, Kenta Nakai, Tetsuya Hayashi, Hitomi Mimuro

    Biochemical and Biophysical Research Communications     2020.5

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  8. Bacteria-Induced Group 2 Innate Lymphoid Cells in the Stomach Provide Immune Protection through Induction of IgA Reviewed Open Access

    Naoko Satoh-Takayama, Tamotsu Kato, Yasutaka Motomura, Tomoko Kageyama, Naoko Taguchi-Atarashi, Ryo Kinoshita-Daitoku, Eisuke Kuroda, James P. Di Santo, Hitomi Mimuro, Kazuyo Moro, Hiroshi Ohno

    Immunity     2020.4

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  9. Complete Genome Sequence of Helicobacter pylori Strain ATCC 43504, a Type Strain That Can Infect Gerbils Reviewed Open Access

    Ryo Kinoshita-Daitoku, Yoshitoshi Ogura, Kotaro Kiga, Fumito Maruyama, Tomoyo Kondo, Ichiro Nakagawa, Tetsuya Hayashi, Hitomi Mimuro

    Microbiology Resource Announcements     2020.4

  10. Ozone ultrafine bubble water induces the cellular signaling involved in oxidative stress responses in human periodontal ligament fibroblasts Reviewed Open Access

    Anongwee Leewananthawet, Shinichi Arakawa, Tokuju Okano, Ryo Daitoku Kinoshita, Hiroshi Ashida, Yuichi Izumi, Toshihiko Suzuki

    Science and Technology of Advanced Materials     2019.12

  11. Inflammasome activation induced by perfringolysin o of clostridium perfringens and its involvement in the progression of gas gangrene Reviewed Open Access

    Kiyonobu Yamamura, Hiroshi Ashida, Tokuju Okano, Ryo Kinoshita-Daitoku, Shiho Suzuki, Kaori Ohtani, Miwako Hamagaki, Tohru Ikeda, Toshihiko Suzuki

    Frontiers in Microbiology     2019

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Books 1

  1. 細胞

    木下 遼

    ニューサイエンス社  2022 

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    Total pages:4  

    CiNii Research

Presentations 1

  1. sRNA regulates pathogenicity during persistent infection of Helicobacter Invited

    2020.2.21 

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 細菌のコントロール:Ωシステムを利用した次世代治療薬の創製

    Grant number:24K02686  2024.4 - 2027.3

    科学研究費助成事業  基盤研究(B)

    木下 遼, 氣駕 恒太朗

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    Authorship:Principal investigator 

    Grant amount:\18590000 ( Direct Cost: \14300000 、 Indirect Cost:\4290000 )

    ヒトの腸内には約1000種類、100兆個以上の細菌が生息しており、腸内細菌叢と呼ばれている。腸内細菌叢の乱れに関連する疾患として偽膜性腸炎、難治性疾患である炎症性腸疾患などが報告されている。しかし、確立された治療法はまだない。そのため、生体内の細菌を特異的かつ持続的にコントロールする技術が求められている。申請者はこれまで細菌を特異的に殺菌できるシステムを探索してきた。その結果、RNA誘導型ヌクレアーゼが標的細菌を狙って特異的に殺菌できることを発見した。そこで本研究では、RNA誘導型ヌクレアーゼを細菌へ供給する遺伝子標的型治療薬の開発を企画した。
    ヒトの腸内には約1000種類、100兆個以上の細菌が生息しており、腸内細菌叢と呼ばれている。腸内細菌は、私たちの作り出すことのできない物質の産生、エネルギーの産生、免疫調整など様々な働きをしている。そのため、腸内細菌叢のバランスの乱れ(dysbiosis)はさまざまな疾患のリスクに直結している。抗生物質の乱用によるdysbiosisは芽胞形成菌のClostridioides difficileによる偽膜性腸炎を引き起こし、腸管接着性侵入性大腸菌(AIEC)の増殖によるdysbiosisは難治性疾患である炎症性腸疾患(潰瘍性大腸炎、クローン病)に関与することが報告されている。これらから、抗菌薬に頼らないバクテリオシンなどの抗菌活性を有する低分子化合物による治療、糞便微生物移植治療(FMT)が行われてきた。しかし、化合物の開発や進化する細菌への適応・改良は困難であり、FMTにより他の感染症が引き起こされた報告もある。そこで申請者は、RNA誘導型ヌクレアーゼを用いて、特定の遺伝子を保有する細菌のみを特異的に狙い撃ちする遺伝子標的型治療薬の研究開発を行うことにした。
    当該年度では、新規RNA誘導型ヌクレアーゼの人工合成を行った。各種RNA誘導型ヌクレアーゼ発現プラスミドを用いて、標的細菌の遺伝子配列特異的な殺菌を解析した。また、標的遺伝子を切断する最適な配列認識RNA(gRNA)の探索を行った。
    各種RNA誘導型ヌクレアーゼの殺菌活性を確認できている。また、標的遺伝子配列を効率よく切断する配列認識RNA(gRNA)の探索に成功している。そのため、本研究課題はおおむね順調に進んでいる。
    研究はおおむね順調に進んでいるため、当初の研究方針から変更はないが、遺伝子標的型治療薬のさまざまな細菌への治療応用を考え、臨床分離株の収集を行う予定である。

  2. Investigating Bacterial Dynamics and Developing New Antimicrobial Agents in Cambodia Using Innovative Genome Analysis Techniques

    Grant number:23KK0151  2023.9 - 2027.3

    Grants-in-Aid for Scientific Research  Fund for the Promotion of Joint International Research (International Collaborative Research)

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    Authorship:Coinvestigator(s) 

  3. Analysis of the mechanism of gastric inflammation induced by small RNAs of H. pylori.

    Grant number:20K16244  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Kinoshita-Daitoku Ryo

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    Helicobacter pylori (H. pylori) infection is known to be involved in the development of gastrointestinal diseases such as gastritis, gastric ulcer, gastric cancer, and MALT lymphoma. In this study, we found that sRNA-X and sRNA-Z possessed by H. pylori are involved in the development of gastritis. Furthermore, we found that the expression levels of sRNA-X correlated with clinical findings based on the results of experiments using clinical isolates of H. pylori. These results indicate that the pathogenic sRNAs possessed by H. pylori contribute to gastritis caused by H. pylori.