Horizontal Transfer of <i>bla</i> <sub>CMY</sub> -Bearing Plasmids among Clinical <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Isolates and Emergence of Cefepime-Hydrolyzing CMY-19

  • Jun-ichi Wachino
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo
  • Hiroshi Kurokawa
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo
  • Satowa Suzuki
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo
  • Kunikazu Yamane
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo
  • Naohiro Shibata
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo
  • Kouji Kimura
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo
  • Yasuyoshi Ike
    Department of Bacteriology and Bacterial Infection Control, Gunma University Graduate School of Medicine, Gunma, Japan
  • Yoshichika Arakawa
    Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo

抄録

<jats:title>ABSTRACT</jats:title> <jats:p> Nine <jats:italic>Escherichia coli</jats:italic> and 5 <jats:italic>Klebsiella pneumoniae</jats:italic> clinical isolates resistant to various cephalosporins and cephamycins were identified in a Japanese general hospital between 1995 and 1997. All nine <jats:italic>E. coli</jats:italic> isolates and one <jats:italic>K. pneumoniae</jats:italic> isolate carried <jats:italic>bla</jats:italic> <jats:sub>CMY-9</jats:sub> , while the other four <jats:italic>K. pneumoniae</jats:italic> isolates harbored a variant of <jats:italic>bla</jats:italic> <jats:sub>CMY-9</jats:sub> , namely, <jats:italic>bla</jats:italic> <jats:sub>CMY-19</jats:sub> . The pulsed-field gel electrophoresis patterns of the nine CMY-9-producing <jats:italic>E. coli</jats:italic> isolates were almost identical, suggesting their clonal relatedness, while those of the five <jats:italic>K. pneumoniae</jats:italic> isolates were divergent. Plasmid profiles, Southern hybridization, and conjugation assays revealed that the genes for the CMY-9 and the CMY-19 β-lactamases were located on very similar conjugative plasmids in <jats:italic>E. coli</jats:italic> and <jats:italic>K. pneumoniae</jats:italic> . The genetic environment of <jats:italic>bla</jats:italic> <jats:sub>CMY-19</jats:sub> was identical to that of <jats:italic>bla</jats:italic> <jats:sub>CMY-9</jats:sub> . A single amino acid substitution, I292S, adjacent to the H-10 helix region was observed between CMY-9 and CMY-19. This substitution was suggested to be responsible for the expansion of the hydrolyzing activity against several broad-spectrum cephalosporins, and this finding was consistent with the kinetic parameters determined with purified enzymes. These findings suggest that the <jats:italic>bla</jats:italic> <jats:sub>CMY-19</jats:sub> genes found in the four <jats:italic>K. pneumoniae</jats:italic> isolates might have originated from <jats:italic>bla</jats:italic> <jats:sub>CMY-9</jats:sub> gene following a point mutation and dispersed among genetically different <jats:italic>K. pneumoniae</jats:italic> isolates via a large transferable plasmid. </jats:p>

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