Adaptation of Escherichia coli to ciprofloxacin and enrofloxacin: Differential proteomics of the SOS response and RecA-independent mechanisms
Artikel i vetenskaplig tidskrift, 2025

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.

Evolutionary adaptation

Fluoroquinolones

Proteomics

RecA

Författare

Lisa Teichmann

Swammerdam Institute for Life Sciences

Raymond Pasman

Swammerdam Institute for Life Sciences

Sam Luitwieler

Swammerdam Institute for Life Sciences

Chiara Varriale

Swammerdam Institute for Life Sciences

Johan Bengtsson Palme

Chalmers, Life sciences, Systembiologi

Göteborgs universitet

Benno Ter Kuile

Swammerdam Institute for Life Sciences

International Journal of Antimicrobial Agents

0924-8579 (ISSN) 1872-7913 (eISSN)

Vol. 65 2 107420

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Stiftelsen för Strategisk forskning (SSF) (FFL21-0174), 2022-08-01 -- 2027-12-31.

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Vetenskapsrådet (VR) (2023-01721), 2023-12-01 -- 2026-11-30.

Etablering av normalnivåer för antibiotikaresistens i olika miljöer för miljöövervakning

Vetenskapsrådet (VR) (2019-00299), 2022-05-01 -- 2023-12-31.

Ämneskategorier (SSIF 2025)

Mikrobiologi inom det medicinska området

DOI

10.1016/j.ijantimicag.2024.107420

PubMed

39742892

Relaterade dataset

URI: https://massive.ucsd.edu/

Mer information

Senast uppdaterat

2025-01-20