The negligible mutagenic effects of norfloxacin on the genome of the fission yeast Schizosaccharomyces pombe ATCC-16979.

Abstract

Antibiotic therapy is commonly used in various medical scenarios, and some antibiotics will stay in the blood serum for days. Previous studies have demonstrated that the fluoroquinolone antibiotic norfloxacin exerts mutagenic effects on the whole genomes of target bacteria. However, whether and to what degree these effects compromise non-target eukaryotic genomes remains unclear. Here, we explored this using mutation accumulation experiments with the fission yeast Schizosaccharomyces pombe ATCC-16979, treated with or without norfloxacin at a dose comparable to the therapeutic concentration found in patient blood. Based on a de novo assembly and the mutation accumulation lines without treatment, ATCC-16979 demonstrates a strong mutation bias in the A/T direction (4.33). Furthermore, norfloxacin treatment did not significantly elevate the genomic mutation rate of the fission yeast, based on the analysis of 94 mutation accumulation lines run for ~169,000 cell divisions in total. Nucleotide excision repair was induced by the norfloxacin treatment and might help to counteract the possible mutagenic effects of norfloxacin, as revealed by RNAseq-based differential gene-expression analyses. Norfloxacin thus poses a negligible genotoxic threat to eukaryotic and potentially human genomes, bolstering the safe clinical use of this important antibiotic.IMPORTANCEThis study addresses concerns about the potential mutagenic side effects of antibiotics, specifically norfloxacin, which is widely used in clinical settings. While previous research has shown that norfloxacin can cause mutations in bacteria, it was unclear whether it could also harm human or other eukaryotic genomes. By using the fission yeast Schizosaccharomyces pombe as a model, we found that norfloxacin treatment did not significantly increase the mutation rate in eukaryotic cells, possibly resulting from a cellular repair mechanism counteracting potential DNA damage. These findings provide reassurance that, at therapeutic levels, norfloxacin does not pose a significant genetic risk to eukaryotic organisms, supporting its continued safe use in medical treatments.