title: Intrapopulation variability in mutator prevalence among urinary tract infection isolates of Escherichia coli.
abstract: Bacteria with elevated mutation rates represent a risk factor for treatment failure and are often found with high frequency in clinical isolates from different sources. How this frequency reflects the among-population and within-population proportion of hypermutators is unknown, despite its importance to the choice of antibiotic therapies that minimize the likelihood of resistance development. Here we screened for hypermutators among the urine of 80 patients with urinary tract infections, at an unprecedented resolution of 24 isolates per sample. We found hypermutators in four patients (5%), at frequencies ranging from 4.2% to 62.5%. Molecular characterization revealed alterations in the oxidized guanine (GO) and methly-directed mistmatch repair (MMR) systems as the genetic basis of hypermutability. These observations suggest that mutators may be present in more patients than previously anticipated, at frequencies that are difficult to detect but still sufficient to impact on adaptation to antibiotics or the host environment.
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain; Unité Mixte de Recherche 1137 (IAME-INSERM), Paris, France. Electronic address: alejandro.couce@inserm.fr.
authors.forename: A
authors.initials: A
authors.lastname: Couce
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain; Institut Pasteur, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Alonso-Rodriguez
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain; Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Costas
authors.affiliation: Hospital Son Dureta (IUNICS), Palma de Mallorca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Oliver
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain; Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Blázquez
mesh_terms: D045643:DNA Repair Enzymes / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000302:isolation & purification*; D004927:Escherichia coli Infections / Q000382:microbiology*; D006801:Humans; D009154:Mutation; D015995:Prevalence; D014552:Urinary Tract Infections / Q000382:microbiology*
chemical_list: D045643:DNA Repair Enzymes
keywords: Antibiotic resistance; hypermutability; mutL; mutY; mutator