Contribution of the SOS response and the DNA repair systems to norfloxacin induced mutations in E. coli

Abstract Antibiotic-resistant bacteria severely threaten human health. Besides spontaneous mutations generated by endogenous factors, the resistance might also originate from induced certain antibiotics, such as fluoroquinolones. Such antibiotics increase genome-wide mutation rate introducing replication errors SOS response pathway or decreasing efficiency of DNA repair systems. However, relative contributions these molecular mechanisms remain unclear, hindering understanding generation resistant pathogens. Here, using newly-accumulated wild-type and SOS-uninducible Escherichia coli strains, well those strains deficient for mismatch (MMR) oxidative damage pathways, we find that is major mutagenesis contributor in elevation, responsible ~ 30–50% total base-pair substitution (BPS) mutation-rate elevation upon treatment with sublethal levels norfloxacin (0 50 ng/mL). We further estimate significance effects on other mutational features (i.e., transversions, structural variations, spectrum) E. linear models. The plays a positive role all three (mutation rates BPSs, variations) affects spectrum. systems significantly reduce BPS transversion rate, regardless whether are present, while increasing variation . Our results quantitatively disentangle antibiotic-induced mutagenesis.