Related Experiment Videos
Correlation between umuC induction and Salmonella mutagenicity assay for quinolone antimicrobial agents
1Department of Microbiology, UMDS, St. Thomas' Hospital, London, UK.
Abstract:
Quinolone antimicrobial agents induce the SOS response in bacteria, including the umuDC genes necessary for error-prone repair. Consequently these drugs may be mutagenic in bacteria with a functional SOS response. Differential killing tests with Escherichia coli WP2 (trp) and its repair-deficient derivative CM871 (trp lexA recA uvrA) indicated that a functional DNA repair system was protective against the action of quinolones, implying that quinolones are causing some form of DNA damage (not necessarily directly) and are therefore genotoxic. Dose-dependent reversion from His- to His+ with quinolones was observed in the Ames test with Salmonella typhimurium TA102 (uvr+) but in no other Salmonella tester strains (all uvr-), suggesting that a functional excision repair system is essential for quinolone-induced bacterial mutagenesis. A significant correlation between SOS inducing potential (SOSIP) and mutagenic potential in the Ames test (r = 0.89) indicated that quinolone-induced mutagenic effects in bacteria are almost entirely due to SOS-processed DNA damage.
Insights
Quinolone antimicrobials can be mutagenic by triggering the SOS response in bacteria, a DNA repair process. This genotoxic effect is linked to DNA damage and requires functional repair systems for mutagenesis.
Area of Science:
- Microbiology
- Genetics
- Toxicology
Background:
- Quinolone antimicrobials are known to induce the bacterial SOS response.
- The SOS response involves genes like umuDC, crucial for error-prone DNA repair.
- This suggests quinolones may possess mutagenic properties in bacteria with an active SOS system.
Purpose of the Study:
- To investigate the genotoxicity of quinolone antimicrobial agents.
- To determine the role of bacterial DNA repair mechanisms in quinolone-induced mutagenesis.
- To correlate the SOS-inducing potential with mutagenic effects.
Main Methods:
- Differential killing assays using Escherichia coli strains with varying DNA repair capabilities.
- Ames test using Salmonella typhimurium strains, including those with functional and deficient excision repair systems.
- Quantification of SOS-inducing potential (SOSIP) and mutagenic potential.
Main Results:
- A functional DNA repair system in E. coli provided protection against quinolones, indicating genotoxicity.
- Quinolones induced dose-dependent mutations in Salmonella typhimurium TA102 (uvr+) but not in uvr- strains.
- A strong positive correlation (r = 0.89) was found between SOS-inducing potential and mutagenic potential in the Ames test.
Conclusions:
- Quinolone antimicrobials are genotoxic to bacteria, causing DNA damage that elicits the SOS response.
- Functional excision repair is essential for quinolone-induced bacterial mutagenesis.
- The mutagenic effects of quinolones in bacteria are primarily mediated by SOS-processed DNA damage.