基本情報

所属
学校法人修文学院 修文大学 医療科学部 臨床検査学科 教授
(兼任) 名古屋大学 医学部/大学院医学系研究科 招へい教員(非常勤講師)
東海国立大学機構 名古屋大学 名誉教授
厚生労働省 国立感染症研究所 名誉所員
学位
医学博士(1989年3月 名古屋大学)

研究者番号
10212622
J-GLOBAL ID
201101032201306103
Researcher ID
P-5997-2015

In the 1980s, I initiated the analyses of a chromosomal genetic region (cps cluster) that is responsible for biosynthesis of K2 capsular polysaccharide in Klebsiella pneumoniae strain Chedid, as well as the characterization of chromosomally encoded β‐lactamase LEN-1 of K. pneumoniae strain LEN-1.  My collaborators and I firstly succeeded in the expression of K2 capsular polysaccharide of strain Chedis in an Escherichia coli K12 by introduction of an about 24-kb chromosomal DNA fragment of Chedid.   We also found that several regulatory proteins, chromosomal RcsA and RcsB, as well as plasmid mediated RmpA2, were involved in the expression of the cps clusters of K. pneumoniae Chedid.

   As for the characterization of β‐lactamase LEN-1 produced by  K. pneumoniae strain LEN-1, we found that the amino acid sequence of 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 KOXY β‐lactamase (or K1 β‐lactamase) of Klebsiella oxytoca was found to belong to the class A β‐lactamases that include LEN‐1 and TEM‐1, although KOXY can effectively 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 (CPE). 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, e.g., plasmid-mediated FosA3 of E. coli and chromosomally-encoded FosK in Acinetobacter soli.

   We also characterized the penicillin-reduced susceptible Streptococcus agalactiae (PRGBS) for the first time, together with macrolide‐resistant Mycoplasma pneumoniae, Campylobacter jejuni, and Helicobacter pylori, as well as carbapenem‐resistant Haemophilus influenzae.

   At present, my research group is involved with the researches and developments of inhibitors for MBLs to overcome the urgent AMR issues by the support of AMED (Japan Agency for Medical Research and Development).


論文

  281

MISC

  1082

書籍等出版物

  26

講演・口頭発表等

  97

所属学協会

  6

共同研究・競争的資金等の研究課題

  29

産業財産権

  20