Effect of D240G substitution in a novel ESBL CTX-M-27

J Antimicrob Chemother. 2003 Jul;52(1):29-35. doi: 10.1093/jac/dkg256. Epub 2003 May 29.

Abstract

Escherichia coli clinical strain Gre-1 collected in 2000 from a French hospital harboured a novel CTX-M-encoding gene, designated blaCTX-M-27. CTX-M-27 differed from CTX-M-14 only by the substitution D240G and was the third CTX-M enzyme harbouring this mutation after CTX-M-15 and CTX-M-16. The Gly-240-harbouring enzyme CTX-M-27 conferred to E. coli higher MICs of ceftazidime (MIC, 8 versus 1 mg/L) than did the Asp-240-harbouring CTX-M-14 enzyme. Comparison of CTX-M-14 and CTX-M-27 showed that residue Gly-240 decreased Km for ceftazidime (205 versus 940 microM), but decreased hydrolytic activity against good substrates, such as cefotaxime (kcat, 113 versus 415 s-1), probably owing to the alteration of beta3 strand positioning during the catalytic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Anti-Bacterial Agents / pharmacology
  • Cloning, Molecular
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Humans
  • Isoelectric Focusing
  • Kinetics
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism*
  • beta-Lactams

Substances

  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • beta-Lactams
  • CTX-M-27, E coli
  • beta-Lactamases