title: Molecular mechanisms of cefoxitin resistance in Escherichia coli from the Toronto area hospitals.
abstract: Escherichia coli may become resistant to cephamycines and oxyimino cephalosporins by virtue of promotor and attenuator mutations or because they have acquired mobilized beta-lactamases from other gram-negative bacilli. This study examined Canadian strains to determine how often promotor and/or attenuator mutations account for this mechanism of resistance and the extent to which clonal spread of these organisms has occurred. We sequenced the promotor and attenuator region of 30 strains resistant to cefoxitin. Twenty-two strains had promotor mutations, 26 had attenuator mutations. Most promotor mutations resulted either in a change in the -35 promotor region towards the E. coli sigma 70 consensus sequence or in the creation of a new consensus hexamer upstream. Eight strains had mutations that increased the typical ampC 16-nucleotide spacer region to the consensus 17- or an 18-nucleotide sequence. Of the attenuator mutations, most did not substantially affect the attenuator loop. Several of the mutations have previously been described in South Africa, Scandinavia, and France. There was evidence that strains bearing certain mutations were clonally disseminated; however, the 11 strains bearing a complex set of attenuator mutations were not. The majority of cephamycin resistant E. coli strains in Toronto have attenuator and/or promotor mutations upstream of the chromosomal ampC gene.
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada. plmkrf@qe2-hsc.ns.ca
authors.forename: K R
authors.initials: KR
authors.lastname: Forward
authors.forename: B M
authors.initials: BM
authors.lastname: Willey
authors.forename: D E
authors.initials: DE
authors.lastname: Low
authors.forename: A
authors.initials: A
authors.lastname: McGeer
authors.forename: M A
authors.initials: MA
authors.lastname: Kapala
authors.forename: M M
authors.initials: MM
authors.lastname: Kapala
authors.forename: L L
authors.initials: LL
authors.lastname: Burrows
mesh_terms: D002440:Cefoxitin / Q000494:pharmacology*; D002513:Cephamycins / Q000494:pharmacology*; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000032:analysis; D016521:Electrophoresis, Gel, Pulsed-Field; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology; D005798:Genes, Bacterial; D006801:Humans; D009154:Mutation; D009864:Ontario / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018440:beta-Lactam Resistance / Q000235:genetics*
chemical_list: D002513:Cephamycins; D004269:DNA, Bacterial; D002440:Cefoxitin