Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response

Abstract Background Fluoroquinolones are indispensable antibiotics used in treating bacterial infections in both human and veterinary medicine. However, resistance to these drugs presents a growing challenge. The SOS response, a DNA repair pathway activated by DNA damage, is known to influence resis...

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Main Authors: Lisa Teichmann, Sam Luitwieler, Johan Bengtsson-Palme, Benno ter Kuile
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Microbiology
Subjects:
Online Access:https://doi.org/10.1186/s12866-025-03771-5
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author Lisa Teichmann
Sam Luitwieler
Johan Bengtsson-Palme
Benno ter Kuile
author_facet Lisa Teichmann
Sam Luitwieler
Johan Bengtsson-Palme
Benno ter Kuile
author_sort Lisa Teichmann
collection DOAJ
description Abstract Background Fluoroquinolones are indispensable antibiotics used in treating bacterial infections in both human and veterinary medicine. However, resistance to these drugs presents a growing challenge. The SOS response, a DNA repair pathway activated by DNA damage, is known to influence resistance development, yet its role in fluoroquinolone resistance is not fully understood. This study aims to unfold the mechanisms of fluoroquinolone resistance by investigating the impact of the SOS response on bacterial adaptation. Results We exposed Escherichia coli to four fluoroquinolones—ciprofloxacin, enrofloxacin, levofloxacin, and moxifloxacin. Using a recA knockout mutant, deficient in the SOS response, as a control, we assessed how the presence or absence of this pathway affects resistance development. Our findings demonstrated that the rate of resistance evolution varied between the different fluoroquinolones. Ciprofloxacin, enrofloxacin, and moxifloxacin exposures led to the most evident reliance on the SOS response for resistance, whereas levofloxacin exposed cultures showed less dependency. Whole genome analysis indicated distinct genetic changes associated with each fluoroquinolone, highlighting potential different pathways and mechanisms involved in resistance. Conclusions This study shows that the SOS response plays a crucial role in resistance development to certain fluoroquinolones, with varying dependencies per drug. The characteristic impact of fluoroquinolones on resistance mechanisms emphasizes the need to consider the unique properties of each antibiotic in resistance studies and treatment strategies. These findings are essential for improving antibiotic stewardship and developing more effective, tailored interventions to combat resistance.
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spelling doaj-art-3abe77e363864bbd9e428aa444ba4e142025-01-26T12:17:54ZengBMCBMC Microbiology1471-21802025-01-0125111110.1186/s12866-025-03771-5Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-responseLisa Teichmann0Sam Luitwieler1Johan Bengtsson-Palme2Benno ter Kuile3University of Amsterdam, Swammerdam Institute of Life Sciences, Molecular Biology and Microbial Food SafetyUniversity of Amsterdam, Swammerdam Institute of Life Sciences, Molecular Biology and Microbial Food SafetyDepartment of Life Sciences, SciLifeLab, Division of Systems and Synthetic Biology, Chalmers University of TechnologyUniversity of Amsterdam, Swammerdam Institute of Life Sciences, Molecular Biology and Microbial Food SafetyAbstract Background Fluoroquinolones are indispensable antibiotics used in treating bacterial infections in both human and veterinary medicine. However, resistance to these drugs presents a growing challenge. The SOS response, a DNA repair pathway activated by DNA damage, is known to influence resistance development, yet its role in fluoroquinolone resistance is not fully understood. This study aims to unfold the mechanisms of fluoroquinolone resistance by investigating the impact of the SOS response on bacterial adaptation. Results We exposed Escherichia coli to four fluoroquinolones—ciprofloxacin, enrofloxacin, levofloxacin, and moxifloxacin. Using a recA knockout mutant, deficient in the SOS response, as a control, we assessed how the presence or absence of this pathway affects resistance development. Our findings demonstrated that the rate of resistance evolution varied between the different fluoroquinolones. Ciprofloxacin, enrofloxacin, and moxifloxacin exposures led to the most evident reliance on the SOS response for resistance, whereas levofloxacin exposed cultures showed less dependency. Whole genome analysis indicated distinct genetic changes associated with each fluoroquinolone, highlighting potential different pathways and mechanisms involved in resistance. Conclusions This study shows that the SOS response plays a crucial role in resistance development to certain fluoroquinolones, with varying dependencies per drug. The characteristic impact of fluoroquinolones on resistance mechanisms emphasizes the need to consider the unique properties of each antibiotic in resistance studies and treatment strategies. These findings are essential for improving antibiotic stewardship and developing more effective, tailored interventions to combat resistance.https://doi.org/10.1186/s12866-025-03771-5FluoroquinolonesAntibiotic resistanceDe novo resistanceSOS responseExperimental evolution
spellingShingle Lisa Teichmann
Sam Luitwieler
Johan Bengtsson-Palme
Benno ter Kuile
Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response
BMC Microbiology
Fluoroquinolones
Antibiotic resistance
De novo resistance
SOS response
Experimental evolution
title Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response
title_full Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response
title_fullStr Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response
title_full_unstemmed Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response
title_short Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response
title_sort fluoroquinolone specific resistance trajectories in e coli and their dependence on the sos response
topic Fluoroquinolones
Antibiotic resistance
De novo resistance
SOS response
Experimental evolution
url https://doi.org/10.1186/s12866-025-03771-5
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