title: Effect of recA inactivation on mutagenesis of Escherichia coli exposed to sublethal concentrations of antimicrobials.
abstract: OBJECTIVE
  Low concentrations of some antibiotics have been reported to stimulate mutagenesis and recombination, which may facilitate bacterial adaptation to different types of stress, including antibiotic pressure. However, the mutagenic effect of most of the currently used antibiotics remains untested. Furthermore, it is known that in many bacteria, including Escherichia coli, stimulation of mutagenesis is mediated by the SOS response. Thus, blockage or attenuation of this response through the inhibition of RecA has been proposed as a possible therapeutic adjuvant in combined therapy to reduce the ability to generate antibiotic-resistant mutants. The aim of this work was to study the capacity of sublethal concentrations of antimicrobials of different families with different molecular targets to increase the mutant frequency of E. coli, and the effect that inactivation of recA would have on antibiotic-mediated mutagenesis.
  
  
  METHODS
  We tested the mutagenicity of the following antimicrobials: ampicillin; ceftazidime; imipenem; fosfomycin; ciprofloxacin; trimethoprim; sulfamethoxazole; trimethoprim/sulfamethoxazole; colistin; tetracycline; gentamicin; rifampicin; and chloramphenicol.
  
  
  RESULTS
  Eight out of the 13 antimicrobials tested stimulate E. coli mutagenesis (slightly in most cases), with trimethoprim, alone or in combination with sulfamethoxazole, producing the highest effect. Inactivation of recA abolishes the mutagenic effect and also produces increased susceptibility to some of the tested antimicrobials.
  
  
  CONCLUSIONS
  The fact that inactivation of recA reduces mutagenicity and/or increases the activity of a large number of antimicrobials supports the hypothesis that RecA inhibition might have favourable effects on antibiotic therapy.
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología-CSIC, Campus UAM-Cantoblanco, 28049 Madrid, Spain.
authors.forename: Thuy Do
authors.initials: TD
authors.lastname: Thi
authors.forename: Elena
authors.initials: E
authors.lastname: López
authors.forename: Alexandro
authors.initials: A
authors.lastname: Rodríguez-Rojas
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Rodríguez-Beltrán
authors.forename: Alejandro
authors.initials: A
authors.lastname: Couce
authors.forename: Javier R
authors.initials: JR
authors.lastname: Guelfo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Castañeda-García
authors.forename: Jesús
authors.initials: J
authors.lastname: Blázquez
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D011938:Rec A Recombinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D009153:Mutagens; D011938:Rec A Recombinases