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, hisG46, hisC9070, and hisG1775 tar gets) that detects the six possible transitions and transversions [Lev in and Ames (1986): Environ Mutagen 8:9-28] and two additional His(-) strains (hisC3076 and hisD3052 targets) carrying frameshift mutations have been used. Our results indicate that GC-->TA transversions are th e major base-pair substitution induced by ciprofloxacin and that GC--> AT transitions ore also produced, but to a lesser degree. However, we cannot discard the fact that AT-->TA transversions are also induced. I n addition, the data indicate that the mutational specificity of cipro floxacin depends on the location of the target. Intragenic base-pair s ubstitutions are the most frequent mutations at the hisG428 target whe n 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 hav e shown that ciprofloxacin also induces deletions/insertions at the hi sC3076 and hisD3052 frameshift targets. Therefore, this inhibitor of D NA gyrase promotes a wide pattern of mutations including different kin ds of base-pair substitutions, 3 or 6 base-pair deletions, and inserti ons/deletions resulting in frameshifts. All of these mutagenic events require the MucAB proteins involved in the error-prone repair, with th e exception of basepair insertions/deletions at the hisD3052 target, w hich are independent of the presence of plasmid pKM101. (C) 1996 Wiley -Liss, Inc.