Fluoroquinolone-Specific Resistance Trajectories in E. coli and their Dependence on the SOS-Response

Abstract

Fluoroquinolones are essential for treating bacterial infections in both human and veterinary medicine. This study investigates the mechanisms behind acquired resistance to fluoroquinolones with a specific focus on the SOS response - a critical cellular pathway activated by DNA damage. Utilizing an experimental evolution approach, we exposed Escherichia coli to four fluoroquinolones and monitored the adaptation process. A recA knock-out mutant deficient in the SOS response was used as biological control. The emergence of resistance was accompanied by numerous DNA mutations, consisting of some observed often and others that infrequently appeared. Our findings indicate that the development of resistance depends in varying degrees on the SOS response among the tested fluoroquinolones, with notable dissimilarities in clinical resistance development. Resistance developed slowest to ciprofloxacin, then levofloxacin, followed by enrofloxacin, and fastest to moxifloxacin. Genomic analysis revealed distinct mutation profiles in cultures exposed to the tested antimicrobials, emphasizing the unique adaptation strategies of bacteria. This research underscores the importance of recognizing the differences among fluoroquinolones in scientific research and clinical practice.