López Elena, Blázquez Jesús
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología-CSIC, Campus UAM-Cantoblanco, 28049 Madrid, Spain.
Antimicrob Agents Chemother. 2009 Aug;53(8):3411-5. doi: 10.1128/AAC.00358-09. Epub 2009 Jun 1.
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.
据报道，某些抗生素的亚抑制浓度，如氟喹诺酮类，可刺激突变，进而促使细菌适应不同压力，包括抗生素压力。在大肠杆菌中，这种刺激是由通过SOS反应诱导的替代DNA聚合酶介导的。已表明氟喹诺酮环丙沙星的亚致死浓度可刺激大肠杆菌中不同序列之间的重组。然而，环丙沙星对同源序列之间重组的影响及其对SOS的依赖性尚未得到研究。此外，其他抗生素对同源重组的可能影响仍未得到测试。这项工作的目的是研究亚致死浓度的环丙沙星和另外10种抗生素，包括具有不同分子靶点的不同分子家族，对大肠杆菌中DNA同源重组率的影响。所测试的抗生素有环丙沙星、氨苄西林、头孢他啶、亚胺培南、氯霉素、四环素、庆大霉素、利福平、甲氧苄啶、磷霉素和黏菌素。我们的结果表明，只有环丙沙星能持续刺激大肠杆菌中同源序列的染色体内重组能力。基于环丙沙星的刺激发生在明显不会严重损害整个群体活力的浓度和时间，并且它依赖于RecA且部分依赖于SOS诱导。这项工作的主要发现之一是，除了喹诺酮类抗生素外，包括甲氧苄啶（一种已知的SOS反应诱导剂）在内的最常用抗生素中，没有一种对大肠杆菌中的同源重组有明显的副作用。除了一些抗生素对天然感受态物种的致突变性、DNA转移和遗传转化能力的已知影响外，至少对于大肠杆菌来说，同源DNA序列染色体内重组增加的影响可唯一归因于氟喹诺酮类。
