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
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
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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
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基盤研究(B), 日本学術振興会(JSPS), Apr, 2015 - Mar, 2018
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Japan Society for the Promotion of Science, Apr, 2014 - Mar, 2017
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科学研究費助成事業(KAKEN)挑戦的萌芽研究, 日本学術振興会(JSPS), Apr, 2016 - Mar, 2017
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食品健康影響評価技術研究, 内閣府, Apr, 2015 - Mar, 2017
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厚生労働科学研究費補助金, 厚生労働省, Apr, 2015 - Mar, 2017
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Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research, Japan Society for the Promotion of Science, Apr, 2014 - Mar, 2016
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Japan Society for the Promotion of Science, Apr, 2013 - Mar, 2016
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平成25年度 自然科学系学術研究助成, 公益財団法人大幸財団, Apr, 2013 - Mar, 2014
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厚生労働科学研究費補助金 新型インフルエンザ等新興・再興感染症研究, 厚生労働省, Apr, 2009 - Mar, 2012
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Japan Society for the Promotion of Science, 2009 - 2011
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厚生労働科学研究費補助金(厚生労働科研費), 厚生労働省, Apr, 2006 - Mar, 2009
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Japan Society for the Promotion of Science, 2007 - 2009
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Japan Society for the Promotion of Science, 2006 - 2008
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厚生労働科学研究費補助金(厚生労働科研費), 厚生労働省, Apr, 2003 - Mar, 2006
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科学研究費助成事業 特定領域研究, 日本学術振興会, 2004 - 2005
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厚生科学研究費補助金(厚生科研費), 厚生省, Apr, 2000 - Mar, 2003
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Japan Society for the Promotion of Science, 2000 - 2003
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厚生労働科学研究費補助金, 厚生労働省, 2001 - Mar, 2002
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科学技術振興調整費, 科学技術庁研究開発局, 1999 - Mar, 2000
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厚生科学研究費補助金, 厚生省, 1998 - Mar, 2000
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厚生科学研究費補助金 新興・再興感染症研究事業, 厚生省, Apr, 1997 - Mar, 2000
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厚生科学研究費補助金 O-157等新興感染症研究事業, 厚生省, 1996 - Mar, 1997
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厚生科学特別研究事業, 厚生省, 1996 - Mar, 1997
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Japan Society for the Promotion of Science, 1996 - 1997
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科学研究費補助金 一般研究(C), 文部科学省, Apr, 1994 - Mar, 1996
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 1993 - 1995
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科学研究費助成事業, 日本学術振興会, 1989 - 1990