Molecular mechanisms of cefoxitin resistance in Escherichia coli from the Toronto area hospitals

Escherichia coli may become resistant to cephamycines and oxyimino cephalos porins by virtue of promotor and attenuator mutations or because they have acquired mobilized beta -lactamases from other grain-negative bacilli. This study examined Canadian strains to determine how often promotor and/or alt ernator mutations account for this mechanism of resistance and the extent t o which clonal spread of these organisms has occurred. We sequenced the pro motor and attenuator region of 30 strains resistant to cefoxitin. Twenty-tw o strains had promotor mutations, 26 had attenuator mutations. Most promoto r 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 consens us heximer 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 alternator mutations, most did not substantially affect th e attenuator loop. Several of the mutations have previously been described in South Africa, Scandinavia, and France. There was evidence that strains b earing certain mutations were clonally disseminated however, the 11 strains bearing a complex set of attenuator mutations were not. The majority of ce phamycin resistant E. coli strains in Toronto have attenuator and/or promot or mutations upstream of the chromosomal ampC gene. (C) 2001 Elsevier Scien ce Inc. All rights reserved.