Adaptation of Escherichia coli to ciprofloxacin and enrofloxacin: Differential proteomics of the SOS response and RecA-independent mechanisms.

Abstract

Objective: Antibiotic resistance is a growing global healthcare challenge, treatment of bacterial infections with fluoroquinolones being no exception. These antibiotics can induce genetic instability through several mechanisms, one of the most significant being the activation of the SOS response. During exposure to sublethal concentration, this stress response increases mutation rates, accelerating resistance evolution.

Methods: To explore the role of the SOS response in fluoroquinolone adaptation, we induced de novo resistance by exposure to step-wise increasing concentrations Escherichia coli wild-type (MG1655) and a ΔrecA mutant strain, which is deficient in SOS activation. Both strains were exposed to stepwise increasing concentrations of ciprofloxacin and enrofloxacin - two fluoroquinolones that differ only by a single methyl group.

Results: Development of resistance against both fluoroquinolones was severely hampered in the ΔrecA mutant. While these antibiotics are often assumed to elicit similar cellular responses, our data revealed distinct genomic and adaptive differences. Building on these findings, we performed a comparative proteomics analysis to investigate how E. coli adapts to ciprofloxacin and enrofloxacin at the protein level.

Conclusions: The results demonstrate that the slight structural variation between ciprofloxacin and enrofloxacin leads to unique proteomic adaptations. These findings suggest that even subtle chemical differences can lead to distinct adaptive trajectories and illustrate the flexibility of cellular stress responses.