Effect of ciprofloxacin exposure on DNA repair mechanisms in Campylobacter jejuni.

Ciprofloxacin resistance is common both among animal and human Campylobacter jejuni isolates. Resistant isolates are shown to persist even without selection pressure. To obtain further insight on effects of ciprofloxacin exposure on C. jejuni we compared transcriptional responses of both C. jejuni wild-type strain 81-176 (ciprofloxacin MIC 0.125 mg l(-1)) and its intermediate ciprofloxacin-resistant variant P3 (Asp90→Asn in GyrA) in the absence and presence of ciprofloxacin. Further, we sequenced the genome of P3 and compared the sequence with that of wild-type 81-176. One hour of exposure to 8 mg l(-1) of ciprofloxacin did not decrease the viability of the parent strain 81-176. Transcriptional analysis revealed that ciprofloxacin exposure caused changes in the expression of genes involved in DNA replication and repair. While in the wild-type the exposure caused downregulation of several genes involved in the control of DNA replication and recombination, the genes controlling nucleotide excision repair and DNA modification were upregulated in both the wild-type and P3. In addition, we observed that ciprofloxacin exposure caused upregulation of genes responsible for damage recognition in base excision repair in P3. In contrast, without ciprofloxacin exposure, DNA repair mechanisms were substantially downregulated in P3. The genome sequence of P3 compared to that of the 81-176 parental strain had three non-synonymous substitutions and a deletion, revealing that the resistant variant had maintained genetic integrity. In conclusion, enhanced DNA repair mechanisms under ciprofloxacin exposure might explain maintenance of genomic integrity in ciprofloxacin-resistant variant P3.

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