title: Genomewide overexpression screen for fosfomycin resistance in Escherichia coli: MurA confers clinical resistance at low fitness cost.
abstract: To determine whether the overexpression of chromosomal genes can confer fosfomycin resistance, genomewide screening of a complete set of 5,272 plasmid-expressed open reading frames of Escherichia coli (ASKA collection) was performed. Major results are that (i) no clinical level of resistance is achieved by overexpressing chromosomal genes, except murA; (ii) this level is reached at a low fitness cost; and (iii) this cost is much lower than that imposed by other mutations conferring fosfomycin resistance.
authors.affiliation: Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Couce
authors.forename: Alejandra
authors.initials: A
authors.lastname: Briales
authors.forename: Alexandro
authors.initials: A
authors.lastname: Rodríguez-Rojas
authors.forename: Coloma
authors.initials: C
authors.lastname: Costas
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual
authors.forename: Jesús
authors.initials: J
authors.lastname: Blázquez
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D001692:Biological Transport / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005578:Fosfomycin / Q000494:pharmacology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D056084:Genetic Fitness; D016680:Genome, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005578:Fosfomycin; D019883:Alkyl and Aryl Transferases; C022566:UDP-N-acetylglucosamine 1-carboxyvinyltransferase