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Analysis of the ciprofloxacin-induced mutations in Salmonella typhimurium

✍ Scribed by Berta Clerch; Juan Manuel Bravo; Montserrat Llagostera


Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
596 KB
Volume
27
Category
Article
ISSN
0893-6692

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✦ Synopsis


The mutagenic events induced by ciprofloxacin, a potent antimicrobial agent, have been characterized. For this, a battery of Hismutants of Salmonella typhimurium (hisG428, hisG46, hisC9070, and hisG1775 targets) that detects the six possible transitions and transversions [Levin and Ames (1986): Environ Mutagen 8:9-281 and two additional His-strains (hisC3076 and hisD3052 targets) carrying frameshift mutations have been used. Our results indicate that GC-TA transversions are the maior basepair substitution induced by ci- profloxacin 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. lntragenic base-pair sub-stitutions are the most frequent mutations at the hisG428 target when it is on the chromosome, whereas 3 or 6 basepair deletions are the maior mutagenic events when this target is on the plasmid pAQl . 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 basepair substitutions, 3 or 6 basepair 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 basepair insertions/deletions at the hisD3052 target, which are independent of the presence of plasmid pKMl 01 .


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