title: Genomewide screen for modulators of evolvability under toxic antibiotic exposure.
abstract: Antibiotic resistance is generally selected within a window of concentrations high enough to inhibit wild-type growth but low enough for new resistant mutants to emerge. We studied de novo evolution of resistance to ciprofloxacin in an Escherichia coli knockout library. Five null mutations had little or no effect on intrinsic antibiotic susceptibility but increased the upper antibiotic dosage to which initially sensitive populations could adapt. These mutations affect mismatch repair, translation fidelity, and iron homeostasis.
authors.affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Méhi
authors.forename: Balázs
authors.initials: B
authors.lastname: Bogos
authors.forename: Bálint
authors.initials: B
authors.lastname: Csörgo
authors.forename: Csaba
authors.initials: C
authors.lastname: Pál
mesh_terms: D000220:Adaptation, Biological; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D019143:Evolution, Molecular; D015723:Gene Library; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012641:Selection, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin