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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli

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Rodriguez-Rosado, Ana I. [1] ; Valencia, Estela Ynes [2] ; Rodriguez-Rojas, Alexandro [3] ; Costas, Coloma [1] ; Galhardo, Rodrigo S. [2] ; Rodriguez-Beltran, Jeronimo [1, 4] ; Blazquez, Jesus [5, 6]
Total Authors: 7
[1] Inst Biomed Sevilla IBiS, Seville - Spain
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil
[3] Free Univ Berlin, Inst Biol, Berlin - Germany
[4] Hosp Univ Ramon y Cajal, IRYCIS, Madrid - Spain
[5] CNB, Madrid - Spain
[6] Univ Hosp Virgen del Rocio, Clin Unit Infect Dis Microbiol & Prevent Med, Seville - Spain
Total Affiliations: 6
Document type: Journal article
Source: Journal of Antimicrobial Chemotherapy; v. 74, n. 8, p. 2188-2196, AUG 2019.
Web of Science Citations: 0

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 similar to 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. (AU)

FAPESP's process: 14/15982-6 - Consequences of repair deficiencies in damaged genome
Grantee:Carlos Frederico Martins Menck
Support type: Research Projects - Thematic Grants