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.
1125-
修文大学紀要(CD-ROM), (13) 45-48, Mar, 2022
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日本細菌学雑誌(Web), 75(1), 2020
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日本細菌学雑誌(Web), 75(1), 2020
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日本細菌学雑誌(Web), 75(1), 2020
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Cocarriage of mcr-1 and APEC-associated virulence genes in E. coli isolates from wastewater influent日本細菌学雑誌(Web), 75(1), 2020
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日本細菌学雑誌(Web), 75(1), 2020
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日本細菌学雑誌(Web), 75(1), 2020
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日本臨床微生物学会雑誌, 30(Suppl.1) 262-262, Dec, 2019
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日本臨床微生物学会雑誌, 30(Suppl.1) 219-219, Dec, 2019
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日本臨床微生物学会雑誌, 30(Suppl.1) 234-234, Dec, 2019
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第48回 薬剤耐性菌研究会発表抄録集(2019年11月15日-11月16日:宇奈月、富山), Nov, 2019
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第48回 薬剤耐性菌研究会発表抄録集(2019年11月15日-11月16日:宇奈月、富山), Nov, 2019
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日本細菌学雑誌(Web), 75(1), Nov, 2019
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医学のあゆみ, 269(6) 439-445, May, 2019 Lead author人類が過去半世紀以上にわたり、細菌感染症の治療のために発見、開発、実用化してきた各種の抗生物質や抗菌化学療法剤などの抗菌薬に対し、多剤耐性を獲得した病原菌が世界中に広がり、人々の健康を脅かす現実的な脅威となっている。これには、ヒトの医療現場のみならず畜水産現場においても抗菌性物質を多用してきたことがその背景にある。新規の抗菌薬の開発は経済的な収益性が低いと見なされ、その実用化は大きく滞っている。近年、"最後の頼み綱"(last resort)のひとつと見なされているカルバペネム系抗菌薬とともに、フルオロキノロン系やアミノ配糖体系などの他の複数の系統の抗菌薬に対しても、多剤耐性を獲得した多剤耐性アシネトバクターやカルバペネム耐性腸内細菌科細菌(CRE)が世界を席巻しつつある。WHO(世界保健機構)や各国政府はこの事態を"人類の危機"と見なし、国際的な連携に基づく総合的な対策を講じはじめている。(著者抄録)
Books and Other Publications
27Presentations
108Teaching Experience
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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