ORCID
- Upton, Mathew: 0000-0003-4287-6396
Abstract
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.
DOI
10.1093/jac/dkv066
Publication Date
2015-07-01
Publication Title
J Antimicrob Chemother
Volume
70
Issue
7
First Page
1969
Last Page
1972
Organisational Unit
School of Biomedical Sciences
Keywords
AmpC β-lactamases, E. coli ST131, antibiotic resistance, Artificial Gene Fusion, Cephalosporin Resistance, Chromosomes, Bacterial, DNA, Escherichia coli, Escherichia coli Proteins, Gene Expression Profiling, Genes, Reporter, Interspersed Repetitive Sequences, Polymerase Chain Reaction, Promoter Regions, Genetic, Sequence Analysis, beta-Galactosidase, beta-Lactamases
Recommended Citation
Phan, M. D., Peters, K., Sarkar, S., Forde, B., Lo, A., Stanton-Cook, M., Roberts, L., Upton, M., Beatson, S., & Schembri, M. (2015) 'Third-generation cephalosporin resistance conferred by a chromosomally encoded blaCMY-23 gene in the Escherichia coli ST131 reference strain EC958.', J Antimicrob Chemother, 70(7), pp. 1969-1972. Available at: https://doi.org/10.1093/jac/dkv066
