Systematic research to overcome newly emerged multidrug‐resistant bacteria

AbstractIn 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 t