Analysis of the Ciprofloxacin-induced Mutations in Salmonella Typhimurium

The mutagenic events induced by ciprofloxacin, a potent antimicrobial agent, have been characterized. For this, a battery of His mutants of Salmonella typhimurium (hisG428, his G46, His C9070, and his G1775 targets) that detects the six possible transitions and transversions [Levin and Ames (1986): Environ Mutagen 8:9-28] and two additional His strains (hisC3076 and his D3052 targets) carrying frameshift mutations have been used. Our results indicate that GC-TA transversions are the major base-pair substitution induced by ciprofloxacin and that GC-At transitions are also produced, but to a lesser degree. However, we cannot discard the fact that At-Ta transversions are also induced. In addition, the data indicate that the mutational specificity of ciprofloxacin depends on the location of the target. Intragenic base-pair substitutions are the most frequent mutations at the hisG428 target when it is on the chromosome, whereas 3 or 6 base-pair deletions are the major mutagenic events when this target is on the plasmid pAQ1. We have shown that ciprofloxacin also induces deletions/insertions at the hisC3076 and hisD3052 frameshift targets. Therefore, this inhibitor of DNA gyrase promotes a wide pattern of mutations including different kinds of base-pair substitutions, 3 or 6 base-pair deletions, and insertions/deletions resulting in frameshifts. All of these mutagenic events require the MucAb proteins involved in the error-prone repair, with the exception of base-pair insertions/deletions at the hisD3052 target, which are independent of the presence of plasmid pKM101.