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Analysis of the ciprofloxacin-induced mutations in Salmonella typhimurium
B Clerch1, J M Bravo, M Llagostera
1Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Spain.
Abstract:
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.
Insights
Ciprofloxacin, an antimicrobial, induces various mutations in Salmonella typhimurium, primarily GC-TA transversions and deletions. These mutagenic events depend on target location and often require error-prone DNA repair proteins.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Ciprofloxacin is a widely used antimicrobial agent.
- Understanding its mutagenic potential is crucial for assessing risks.
- DNA gyrase inhibitors like ciprofloxacin can impact bacterial DNA.
Purpose of the Study:
- To characterize the specific mutagenic events induced by ciprofloxacin.
- To investigate the mutational specificity of ciprofloxacin in Salmonella typhimurium.
- To determine the role of DNA repair pathways in ciprofloxacin-induced mutagenesis.
Main Methods:
- Utilized a battery of Salmonella typhimurium His mutants targeting base-pair substitutions and frameshifts.
- Assessed mutations at different genetic loci (chromosome vs. plasmid).
- Investigated the involvement of MucAB error-prone repair proteins.
Main Results:
- Ciprofloxacin primarily induces GC-TA transversions and GC-AT transitions.
- Mutational specificity is target-dependent, with deletions observed at specific loci.
- Most mutations require MucAB proteins, except for some insertions/deletions at the hisD3052 target.
Conclusions:
- Ciprofloxacin is a potent mutagen inducing a broad spectrum of DNA alterations.
- The pattern of ciprofloxacin-induced mutations varies based on target site and context.
- Error-prone repair pathways play a significant role in mediating ciprofloxacin mutagenesis.