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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Antimicrobial Chemotherapy; v. 74, n. 8, p. 2188-2196, AUG 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 14/15982-6 - Consequências de deficiências de reparo de lesões no genoma
• Beneficiário: Carlos Frederico Martins Menck
• Modalidade de apoio: Auxílio à Pesquisa - Temático