Third-generation cephalosporin resistance conferred by a chromosomally encoded blaCMY-23 gene in the Escherichia coli ST131 reference strain EC958

J Antimicrob Chemother. 2015 Jul;70(7):1969-72. doi: 10.1093/jac/dkv066. Epub 2015 Mar 18.


Objectives: Escherichia coli ST131 is a globally disseminated MDR clone originally identified due to its association with the blaCTX-M-15 gene encoding an ESBL. It is thus assumed that blaCTX-M-15 is the major determinant for resistance to β-lactam antibiotics in this clone. The complete sequence of EC958, a reference strain for E. coli ST131, revealed that it contains a chromosomally located blaCMY-23 gene with an upstream ISEcp1 element as well as several additional plasmid-encoded β-lactamase genes. Here, we examined the genetic context of the blaCMY-23 element in EC958 and other E. coli ST131 strains and investigated the contribution of blaCMY-23 to EC958 resistance to a range of β-lactam antibiotics.

Methods: The genetic context of blaCMY-23 and its associated mobile elements was determined by PCR and sequencing. Antibiotic susceptibility testing was performed using Etests. The activity of the blaCMY-23 promoter was assessed using lacZ reporter assays. Mutations were generated using λ-Red-recombination.

Results: The genetic structure of the ISEcp1-IS5-blaCMY-23 mobile element was determined and localized within the betU gene on the chromosome of EC958 and five other E. coli ST131 strains. The transcription of blaCMY-23, driven by a previously defined promoter within ISEcp1, was significantly higher than other β-lactamase genes and could be induced by cefotaxime. Deletion of the blaCMY-23 gene resulted in enhanced susceptibility to cefoxitin, cefotaxime and ceftazidime.

Conclusions: This is the first known report to demonstrate the chromosomal location of blaCMY-23 in E. coli ST131. In EC958, CMY-23 plays a major role in resistance to third-generation cephalosporins and cephamycins.

Keywords: AmpC β-lactamases; E. coli ST131; antibiotic resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Gene Fusion
  • Cephalosporin Resistance*
  • Chromosomes, Bacterial
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Expression Profiling
  • Genes, Reporter
  • Interspersed Repetitive Sequences
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA
  • beta-Galactosidase / analysis
  • beta-Galactosidase / genetics
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*


  • DNA, Bacterial
  • Escherichia coli Proteins
  • beta-Galactosidase
  • beta-Lactamases