Profile Information
- Affiliation
- School of Medicine, Fujita Health UniversityCollege of Pharmacy, Kinjo Gakuin UniversityGraduate School of Medicine, Nagoya UniversityNational Institute of Infectious Diseases名誉教授, 名古屋大学, 東海国立大学機構
- Degree
- 医学博士(Mar, 1989, 名古屋大学)
- Researcher number
- 10212622
- J-GLOBAL ID
- 201101032201306103
- Researcher ID
- P-5997-2015
- researchmap Member ID
- 6000030043
In the 1980s, I found that the chromosomal β‐lactamase of Klebsiella pneumoniae
LEN‐1 showed a very high similarity to the R‐plasmid‐mediated penicillinase
TEM‐1 on the amino acid sequence level, and this strongly suggested the origination
of TEM‐1 from the chromosomal penicillinases of K. pneumoniae or related
bacteria. Moreover, the chromosomal K1 β‐lactamase (KOXY) of Klebsiella oxytoca
was found to belong to the class A β‐lactamases that include LEN‐1 and TEM‐1,
although KOXY can hydrolyze cefoperazone (CPZ) like the chromosomal AmpC type
cephalosporinases of various Enterobacteriaceae that can hydrolyze several
cephalosporins including CPZ. Furthermore, my collaborators and I found plural
novel serine‐type β‐lactamases, such as MOX‐1, SHV‐24, TEM‐91, CTX‐M‐64,
CMY‐9, CMY‐19, GES‐3, GES‐4, and TLA‐3, mediated by plasmids. Besides these
serine‐type β‐lactamases, we also first identified exogenously acquired metallo‐
β‐lactamases (MBLs), IMP‐1 and SMB‐1, in imipenem‐resistant Serratia marcescens,
and the IMP‐1‐producing S. marcescens TN9106 became the index case for
carbapenemase‐producing Enterobacteriaceae. I developed the sodium mercaptoacetic
acid (SMA)‐disk test for the simple identification of MBL‐producing
bacteria. We were also the first to identify a variety of plasmid‐mediated 16S
ribosomal RNA methyltransferases, RmtA, RmtB, RmtC, and NpmA, from various
Gram‐negative bacteria that showed very high levels of resistance to a wide
range of aminoglycosides. Furthermore, we first found plasmid‐mediated quinolone
efflux pump (QepA) and fosfomycin‐inactivating enzymes (FosA3 and FosK).
We also first characterized penicillin reduced susceptible Streptococcus agalactiae (PRGBS),
macrolide‐resistant Mycoplasma pneumoniae, as well as Campylobacter jejuni, and
Helicobacter pylori, together with carbapenem‐resistant Haemophilus influenzae.
Research Interests
2Research Areas
3Major Research History
29-
Apr, 2020 - Present
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Apr, 2020 - Present
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Apr, 2020 - Mar, 2024
Education
3-
Apr, 1985 - Mar, 1989
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Nov, 1984 - Mar, 1985
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Apr, 1975 - Sep, 1983
Committee Memberships
29-
Oct, 2023 - Present
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Mar, 2022 - Present
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Dec, 2016 - Present
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Jul, 2012 - Present
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Apr, 2011 - Present
Awards
3Papers
297-
Antimicrobial Agents and Chemotherapy, 68(4) e0117923, Apr 3, 2024 Peer-reviewedABSTRACT Streptococcus mitis/oralis group isolates with reduced carbapenem susceptibility have been reported, but its isolation rate in Japan is unknown. We collected 356 clinical α-hemolytic streptococcal isolates and identified 142 of them as S. mitis/oralis using partial sodA sequencing. The rate of meropenem non-susceptibility was 17.6% (25/142). All 25 carbapenem-non-susceptible isolates harbored amino acid substitutions in/near the conserved motifs in PBP1A, PBP2B, and PBP2X. Carbapenem non-susceptibility is common among S. mitis/oralis group isolates in Japan.
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Microbiology Spectrum, 12(3) e0234423, Feb 5, 2024The number and type of metallo-β-lactamase (MΒL) are increasing over time. Carbapenem resistance conferred by MΒL is a significant threat to our antibiotic regimen, and the development of MΒL inhibitors is urgently required to restore carbapenem efficacy. Microbial natural products have served as important sources for developing antimicrobial agents targeting pathogenic bacteria since the discovery of antibiotics in the mid-20th century. MΒL inhibitors derived from microbial natural products are still rare compared to those derived from chemical compound libraries. Hydroxyhexylitaconic acids (HHIAs) produced by members of the genus Aspergillus have potent inhibitory activity against clinically relevant IMP-type MBL. HHIAs may be good lead compounds for the development of MBL inhibitors applicable for controlling carbapenem resistance in IMP-type MBL-producing Enterobacterales .
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Japanese Journal of Infectious Diseases, Jan 31, 2024All clinical isolates of Streptococcus dysgalactiae subsp. equisimilis (SDSE) are considered susceptible to β-lactams, the first-line drugs used for SDSE infections. However, penicillin-non-susceptible SDSE has been reported from Denmark. In this study, we attempted to detect β-lactam-non-susceptible clinical isolates of SDSE in Japan. One hundred and fifty clinical isolates of S. dysgalactiae were collected in 2018, and species identification was performed using Rapid ID Strep API. The minimum inhibitory concentrations (MIC) of six β-lactams (penicillin G, oxacillin, ceftizoxime, ceftibuten, cefoxitin, and cefaclor) were determined for 85 clinical isolates of SDSE using the agar dilution method standardized by the Clinical Laboratory Standards Institute. For the 85 isolates identified as SDSE, the MIC ranges of penicillin G, oxacillin, ceftizoxime, ceftibuten, cefoxitin, and cefaclor were 0.007-0.06, 0.03-0.12, 0.015-0.06, 0.25-2, 0.12-2, and 0.06-0.5 μg/mL, respectively. None of the clinical isolates were non-susceptible to penicillin G, indicating that all 85 clinical isolates of SDSE were susceptible to β-lactams. Our findings indicate that almost all clinical isolates of SDSE in several prefectures of Japan remain susceptible to β-lactams. Nevertheless, there remains a need for continuous and careful monitoring of drug susceptibility among clinical isolates of SDSE in Japan.
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Diagnostic microbiology and infectious disease, 105(3) 115881-115881, Mar, 2023We used 73 group B Streptococcus with reduced penicillin susceptibility (PRGBS) isolates and determined more rational cutoff values of previously developed disk diffusion method for detecting PRGBS using oxacillin, ceftizoxime, and ceftibuten disks. Using the novel cutoff values, the three disks showed high sensitivity and specificity, which were above 90.0%.
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Journal of Microbiological Methods, 204 106645-106645, Jan, 2023
Misc.
1125Books and Other Publications
27Presentations
108-
日本医療研究開発機構(AMED); Asian-African Research Forum on Emerging and Reemerging Infections 2019, Sep 5, 2019 Invited
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内閣府食品安全委員会:One-day Workshop for Risk Assessment and Surveillance/Monitoring on Foodborne Antimicrobial Resistance, Dec 4, 2017 Invited
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第87回 日本感染症学会西日本地方会学術集会/第60回 日本感染症学会中日本地方会学術集会/第65回 日本化学療法学会西日本支部総会 合同総会 教育講演1, Oct 26, 2017 Invited
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JSCM 26th Annual Meeting, 2015;Japan-Korea Joint Symposium, Jan 31, 2015 Invited
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英国大使館主催 UK-Japan Workshop on Antimicrobial Resistance (AMR) Session 4 – Basic Science: Mechanisms of Resistance, Nov 10, 2014 Invited
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第63回 日本感染症学会東日本地方会総会学術集会/第61回 日本化学療法学会東日本支部総会 合同総会 特別講演2, Oct 30, 2014 Invited
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Singapore-Japan Joint Forum; Emerging Concepts in Microbiology, Nov 16, 2011 Invited
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IUMS 2011 Sapporo, Sep 8, 2011
Teaching Experience
1-
1989 - Present医学細菌学、病原細菌学、薬剤耐性菌等 (名古屋大学 [医、保健、工]、群馬大学 [医]、千葉大学 [薬]、東京薬科大学 [薬]、愛知学院大学 [歯・薬]、岐阜薬科大学 [薬]、愛知医科大学[医]、 他)
Professional Memberships
6Research Projects
32-
創薬支援推進事業・創薬総合支援事業, 日本医療研究開発機構(AMED), Apr, 2022 - Mar, 2025
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創薬支援推進事業, 日本医療研究開発機構(AMED), Apr, 2020 - Mar, 2022
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創薬総合支援事業, 日本医療研究開発機構(AMED), Jan, 2017 - Dec, 2019
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感染症実用化研究事業, 日本医療研究開発機構(AMED), Apr, 2016 - Mar, 2019
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感染症研究国際展開戦略プログラム(J-GRID), 日本医療研究開発機構(AMED), Oct, 2015 - Mar, 2018