Novel cefotaximase (CTX-M-16) with increased catalytic efficiency due to substitution Asp-240-->Gly

Antimicrob Agents Chemother. 2001 Aug;45(8):2269-75. doi: 10.1128/AAC.45.8.2269-2275.2001.

Abstract

Three clinical strains (Escherichia coli Rio-6, E. coli Rio-7, and Enterobacter cloacae Rio-9) collected in 1996 and 1999 from hospitals in Rio de Janeiro (Brazil) were resistant to broad-spectrum cephalosporins and gave a positive double-disk synergy test. Two bla(CTX-M) genes encoding beta-lactamases of pl 7.9 and 8.2 were implicated in this resistance: the bla(CTX-M-9) gene observed in E. coli Rio-7 and E. cloacae Rio-9 and a novel CTX-M-encoding gene, designated bla(CTX-M-16), observed in E. coli strain Rio-6. The deduced amino acid sequence of CTX-M-16 differed from CTX-M-9 only by the substitution Asp-240-->Gly. The CTX-M-16-producing E. coli transformant exhibited the same level of resistance to cefotaxime (MIC, 16 microg/ml) but had a higher MIC of ceftazidime (MIC, 8 versus 1 microg/ml) than the CTX-M-9-producing transformant. Enzymatic studies revealed that CTX-M-16 had a 13-fold higher affinity for aztreonam and a 7.5-fold higher k(cat) for ceftazidime than CTX-M-9, thereby showing that the residue in position 240 can modulate the enzymatic properties of CTX-M enzymes. The two bla(CTX-M-9) genes and the bla(CTX-M-16) gene were located on different plasmids, suggesting the presence of mobile elements associated with CTX-M-encoding genes. CTX-M-2 and CTX-M-8 enzymes were found in Brazil in 1996, and two other CTX-M beta-lactamases, CTX-M-9 and CTX-M-16, were subsequently observed. These reports are evidence of the diversity of CTX-M-type extended-spectrum beta-lactamases in Brazil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics*
  • Aspartic Acid / genetics
  • Brazil
  • Cefotaxime / pharmacology*
  • Cephalosporin Resistance / genetics*
  • Cephalosporins / pharmacology*
  • DNA, Bacterial / analysis
  • Drug Resistance, Microbial
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology*
  • Enterobacteriaceae / genetics
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Gene Transfer Techniques
  • Glycine / genetics
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Sequence Homology, Amino Acid
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

  • Cephalosporins
  • DNA, Bacterial
  • Aspartic Acid
  • beta-lactamase CTX-2
  • beta-Lactamases
  • Cefotaxime
  • Glycine