Background: Fluoroquinolones such as ciprofloxacin induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS). Both the SOS response and ROS increase bacterial mutagenesis, fuelling the emergence of resistant mutants during antibiotic treatment. Recently, there has been growing interest in developing new drugs able to diminish the mutagenic effect of antibiotics by modulating ROS production and the SOS response.
Objectives: To test whether physiological concentrations of N-acetylcysteine, a clinically safe antioxidant drug currently used in human therapy, is able to reduce ROS production, SOS induction and mutagenesis in ciprofloxacin-treated bacteria without affecting antibiotic activity.
Methods: The Escherichia coli strain IBDS1 and its isogenic mutant deprived of SOS mutagenesis (TLS-) were treated with different concentrations of ciprofloxacin, N-acetylcysteine or both drugs in combination. Relevant parameters such as MICs, growth rates, ROS production, SOS induction, filamentation and antibiotic-induced mutation rates were evaluated.
Results: Treatment with N-acetylcysteine reduced intracellular ROS levels (by ∼40%), as well as SOS induction (by up to 75%) and bacterial filamentation caused by subinhibitory concentrations of ciprofloxacin, without affecting ciprofloxacin antibacterial activity. Remarkably, N-acetylcysteine completely abolished SOS-mediated mutagenesis.
Conclusions: Collectively, our data strongly support the notion that ROS are a key factor in antibiotic-induced SOS mutagenesis and open the possibility of using N-acetylcysteine in combination with antibiotic therapy to hinder the development of antibiotic resistance.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jac/dkz210 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response.
BMC Microbiol
January 2025
University of Amsterdam, Swammerdam Institute of Life Sciences, Molecular Biology and Microbial Food Safety, Amsterdam, The Netherlands.
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.
View Article and Find Full Text PDFVirulent Bacteriophages for Controlling Shiga Toxin-Producing Escherichia coli (STEC) Without Inducing Toxin Production.
J Infect Dis
January 2025
Division of Environmental Health Sciences, School of Public Health, University of Minnesota, St. Paul, MN 55108, USA.
Shiga toxin-producing Escherichia coli (STEC) infections pose a significant public health challenge, characterized by severe complications including hemolytic uremic syndrome (HUS) due to Shiga toxin (Stx) production. Current therapeutic approaches encounter a critical limitation, as conventional antibiotic treatment is contraindicated due to its propensity to trigger bacterial SOS response and subsequently enhance Stx production, which increases the likelihood of developing HUS in antibiotic-treated patients. The lack of effective, safe therapeutic options has created an urgent need for alternative treatment strategies for STEC infections.
View Article and Find Full Text PDFReplisomal coupling between the α-Pol III core and the τ-subunit of the clamp loader complex (CLC) are essential for genomic integrity in E. coli.
J Biol Chem
January 2025
Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, 76798-7348, USA. Electronic address:
Coupling interactions between the alpha (α) subunit of the polymerase III core (α-Pol III core) and the tau (τ) subunit of the clamp loader complex (τ-CLC) are vital for efficient and rapid DNA replication in Escherichia coli (E. coli). Specific and targeted mutations in the C-terminal τ-interaction region of the Pol III α-subunit disrupted efficient coupled rolling circle DNA synthesis in vitro and caused significant genomic defects in CRISPR-Cas9 dnaE edited cell strains.
View Article and Find Full Text PDFThe SOS Response Activation and the Risk of Antibiotic Resistance Enhancement in spp. Strains Exposed to Subinhibitory Concentrations of Ciprofloxacin.
Int J Mol Sci
December 2024
Department of Biology of Bacteria, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland.
The widespread and inappropriate use of antibiotics, for therapeutic and prophylactic purposes, has contributed to a global crisis of rapidly increasing antimicrobial resistance of microorganisms. This resistance is often associated with elevated mutagenesis induced by the presence of antibiotics. Additionally, subinhibitory concentrations of antibiotics can trigger stress responses in bacteria, further exacerbating this problem.
View Article and Find Full Text PDFGenome-wide identification, characterization, and functional analysis of the CHX, SOS, and RLK genes in Solanum lycopersicum under salt stress.
Sci Rep
January 2025
Department of Plant Genetic Transformation, Agricultural Genetic Engineering Research Institute (AGERI), Agricultural Research Center (ARC), Cairo, Egypt.
The cation/proton exchanger (CHX), salt overly sensitive (SOS), and receptor-like kinase (RLK) genes play significant roles in the response to salt stress in plants. This study is the first to identify the SOS gene in Solanum lycopersicum (tomato) through genome-wide analysis under salt stress conditions. Quantitative reverse transcription PCR (qRT-PCR) results indicated that the expression levels of CHX, SOS, and RLK genes were upregulated, with fold changes of 1.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!