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Antimicrobial Agents and Chemotherapy, August 2009, p. 3411-3415, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00358-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Effect of Subinhibitory Concentrations of Antibiotics on Intrachromosomal Homologous Recombination in Escherichia coli{triangledown}

Elena López and Jesús Blázquez*

Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología-CSIC, Campus UAM—Cantoblanco, 28049 Madrid, Spain

Received 16 March 2009/ Returned for modification 9 May 2009/ Accepted 23 May 2009

Subinhibitory concentrations of some antibiotics, such as fluoroquinolones, have been reported to stimulate mutation and, consequently, bacterial adaptation to different stresses, including antibiotic pressure. In Escherichia coli, this stimulation is mediated by alternative DNA polymerases induced via the SOS response. Sublethal concentrations of the fluoroquinolone ciprofloxacin have been shown to stimulate recombination between divergent sequences in E. coli. However, the effect of ciprofloxacin on recombination between homologous sequences and its SOS dependence have not been studied. Moreover, the possible effects of other antibiotics on homologous recombination remain untested. The aim of this work was to study the effects of sublethal concentrations of ciprofloxacin and 10 additional antibiotics, including different molecular families with different molecular targets, on the rate of homologous recombination of DNA in E. coli. The antibiotics tested were ciprofloxacin, ampicillin, ceftazidime, imipenem, chloramphenicol, tetracycline, gentamicin, rifampin (rifampicin), trimethoprim, fosfomycin, and colistin. Our results indicate that only ciprofloxacin consistently stimulates the intrachromosomal recombinogenic capability of homologous sequences in E. coli. The ciprofloxacin-based stimulation occurs at concentrations and times that apparently do not dramatically compromise the viability of the whole population, and it is dependent on RecA and partially dependent on SOS induction. One of the main findings of this work is that, apart from quinolone antibiotics, none of the most used antibiotics, including trimethoprim (a known inducer of the SOS response), has a clear side effect on homologous recombination in E. coli. In addition to the already described effects of some antibiotics on mutagenicity, DNA transfer, and genetic transformability in naturally competent species, the effect of increasing intrachromosomal recombination of homologous DNA sequences can be uniquely ascribed to fluoroquinolones, at least for E. coli.

* Corresponding author. Mailing address: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología-CSIC, Campus UAM—Cantoblanco, 28049 Madrid, Spain. Phone: 34 91 585 54 33. Fax: 34 91 585 45 06. E-mail: blazquez{at}cnb.csic.es

{triangledown} Published ahead of print on 1 June 2009.

Antimicrobial Agents and Chemotherapy, August 2009, p. 3411-3415, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00358-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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