Antibiotic-mediated recombination: ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli.
The widespread use and abuse of antibiotics as therapeutic agents has produced a major challenge for bacteria, leading to the selection and spread of antibiotic resistant variants. However, antibiotics do not seem to be mere selectors of these variants. Here we show that the fluoroquinolone antibiotic ciprofloxacin, an inhibitor of type II DNA topoisomerases, stimulates intrachromosomal recombination of DNA sequences. The stimulation of recombination between divergent sequences occurs via either the RecBCD or RecFOR pathways and is, surprisingly, independent of SOS induction. Additionally, this stimulation also occurs in a hyperrecombinogenic mismatch repair mutS mutant. It is worth noting that ciprofloxacin also stimulates the conjugational recombination of an antibiotic resistance gene. Finally, we demonstrate that Escherichia coli is able to recover from treatments with recombination-stimulating concentrations of the antibiotic. Thus, fluoroquinolones can increase genetic variation by the stimulation of the recombinogenic capability of treated bacteria (via an SOS-independent mechanism) and consequently may favour the acquisition, evolution and spread of antibiotic resistance determinants.
López
Elena
E
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología-CSIC, Campus UAM-Cantoblanco, 28049-Madrid, Spain.
Elez
Marina
M
Matic
Ivan
I
Blázquez
Jesús
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D003227:Conjugation, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D043211:Exodeoxyribonuclease V / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000187:drug effects*; D013014:SOS Response, Genetics
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C081006:RecO protein, E coli; C489318:RecR protein, E coli; C489340:recF protein, E coli; D002939:Ciprofloxacin; D043211:Exodeoxyribonuclease V; C468322:exodeoxyribonuclease V, E coli