Antibiotic treatment enhances the genome-wide mutation rate of target cells

Significance The evolution of antibiotic resistance by pathogenic bacteria poses a major challenge for human health. Whereas it is clear that natural selection promotes resistance-conferring mutations, our understanding of the response of the mutation rate to antibiotics is limited. With hundreds of Escherichia coli cell lines evolving in a near-neutral scenario under exposure to the fluoroquinolone norfloxacin, this study reveals a significant linear relationship between the mutation rate and antibiotic concentration, while also demonstrating that antibiotic treatment compromises the efficiency of DNA oxidative-damage repair and postreplicative mismatch repair. Thus, antibiotics not only impose a selective challenge to target and off-target bacteria but also accelerate the rate of adaptation by magnifying the rate at which advantageous mutations arise.