title: Antimicrobial Susceptibility and Molecular Mechanisms of Fosfomycin Resistance in Clinical Escherichia coli Isolates in Mainland China.
abstract: Escherichia coli is one of the most common pathogens in nosocomial and community-acquired infections in humans. Fosfomycin is a broad-spectrum antibiotic which inhibits peptidoglycan synthesis responsible for bacterial cell wall formation. Although low, the exact E. coli susceptibility to fosfomycin as well as the mechanisms of resistance in the population from Mainland China are mostly unknown. 1109 non-duplicate clinical E. coli strains isolated from urine, sputum, blood and pus samples in 20 widely dispersed tertiary hospitals from Mainland China were collected from July 2009 to June 2010, followed by determination of minimum inhibitory concentrations of fosfomycin. Detection of the murA, glpT, uhpT, fosA, fosA3 and fosC genes was performed in fosfomycin non-susceptible E. coli strains and conjugation experiments were employed to determine the mobility of fosA3 gene. In this study, 7.8% (86/1109) E. coli strains were fosfomycin non-susceptible. Amino acid substitutions in GlpT and MurA were found in six and four E.coli strains, respectively, while the uhpT gene was absent in eighteen E.coli strains. Twenty-nine isolates carried the transferable plasmid with the fosA3 gene at high frequencies of around 10(-6) to 10(-7) per donor cell in broth mating. The majority of isolates were susceptible to fosfomycin, showing that the drug is still viable in clinical applications. Also, the main mechanism of E. coli resistance in Mainland China was found to be due to the presence of the fosA3 gene.
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, PR of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, PR of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, PR of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biostatistics, Peking University First Hospital, Beijing, PR of China.
authors.forename: Sainan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, PR of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.affiliation: Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, PR of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D020134:Catalytic Domain; D002681:China; D017931:DNA Primers; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics*; D005578:Fosfomycin / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D062606:Tertiary Care Centers
chemical_list: D000890:Anti-Infective Agents; D017931:DNA Primers; D029968:Escherichia coli Proteins; C000607929:FosA(3) protein, E coli; C488962:GlpT protein, E coli; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; C063498:UhpT protein, E coli; D005578:Fosfomycin