title: Mechanism of Reduced Susceptibility to Fosfomycin inEscherichia coliClinical Isolates.
abstract: In recent years, multidrug resistance ofEscherichia colihas become a serious problem. However, resistance to fosfomycin (FOM) has been low. We screenedE. coliclinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC ≥ 8μg/mL) in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fosgenes) and mutations inmurAthat underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6-phosphate (G6P) transporter andsn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P ofuhpTthat encodes G6P transporter expression. Nucleotide sequences of theuhpT,uhpA, glpT,ptsI, andcyaAshared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction ofuhpTfunction is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations inmurA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear.
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan; Department of Clinical Laboratory, NTT East Sapporo Hospital, Chuo-ku, Sapporo 060-0061, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohkoshi
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Soh
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Shiraishi
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ogasawara
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Shin-Ichi
authors.identifier: 0000-0002-0831-3429
authors.initials: SI
authors.lastname: Yokota
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics; D001483:Base Sequence; D018432:Drug Resistance, Multiple / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000235:genetics; D005578:Fosfomycin / Q000008:administration & dosage*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D019298:Glucose-6-Phosphate / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation
chemical_list: D029968:Escherichia coli Proteins; D009004:Monosaccharide Transport Proteins; C063498:UhpT protein, E coli; D005578:Fosfomycin; D019298:Glucose-6-Phosphate; D019883:Alkyl and Aryl Transferases; C022566:UDP-N-acetylglucosamine 1-carboxyvinyltransferase