title: Development of high-level ceftazidime resistance via single-base substitutions of blaCTX-M-3 in hyper-mutable Escherichia coli.
abstract: Mutations can increase the ceftazidimase activity of CTX-M-3 beta-lactamase, as seen with its widespread variant CTX-M-15. This study compared the frequencies of emerging ceftazidime resistance in isogenic wild-type and hyper-mutable mutS CTX-M-3-producing Escherichia coli strains, and sequenced the mutant bla(CTX-M) alleles selected. Ceftazidime resistance emerged more readily in the hyper-mutable background than in the wild-type strain. All selected CTX-M mutants, in both the wild-type and the mutS derivatives, had single amino-acid changes at position 167, including a novel Pro167Gln substitution. These data emphasise the potential for further diversification of CTX-M enzymes.
authors.affiliation: Antibiotic Resistance Monitoring and Reference Laboratory, Centre for Infections, Health Protection Agency, London, UK. edi.karisik@hpa.org.uk
authors.forename: E
authors.initials: E
authors.lastname: Karisik
authors.forename: M J
authors.initials: MJ
authors.lastname: Ellington
authors.forename: R
authors.initials: R
authors.lastname: Pike
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
authors.forename: N
authors.initials: N
authors.lastname: Woodford
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime; C417271:beta-lactamase CTX-M-3; D001618:beta-Lactamases