Emergence of fosfomycin-resistant isolates of shiga-like toxin-producing Escherichia coli O26

We evaluated the susceptibilities of 129 Shiga like toxin-producing Escheri chia coli (STEC) isolates to various antibiotics. The numbers of isolates f or,which MICs were high (greater than or equal to 128 mu g/ml) were as foll ows: 5 for fosfomycin, 14 for ampicillin, 1 for cefaclor, 6 for kanamycin, 22 for tetracycline, and 2 for doxycycline. For two isolates of STEC O26 MI Cs of fosfomycin were high (1,023 and 512 mu g/ml, respectively). Conjugati on experiments and glutathione S-transferase assays suggested that the fosf omycin resistance in these isolates was determined not by a plasmid but chr omosomally, The amount of active intracellular fosfomycin in these STEC iso lates was 100- to 200-fold less than that in E. coli C600 harboring pREFTT4 7B408 in the presence of either L-alpha-glycerophosphate or glucose-6-phosp hate, Cloning, sequencing, and Northern blot analysis demonstrated that the transcriptional level of the murA gene encoding UDP-N-acetylglucosamine en olpyruvoyl transferase in these isolates was greater than that in E. coli C 600. Our results suggest that the fosfomycin resistance in these STEC isola tes is due to concurrent effects of alteration of the glpT and/or uhp trans port systems and of the enhanced transcription of the murA gene.