N-acetylcysteine blocks SOS induction and #mutagenesis produced by #fluoroquinolones in #Escherichia coli (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

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

Ana I Rodríguez-Rosado, Estela Ynés Valencia, Alexandro Rodríguez-Rojas, Coloma Costas, Rodrigo S Galhardo, Jerónimo Rodríguez-Beltrán, Jesús Blázquez

Journal of Antimicrobial Chemotherapy, dkz210, https://doi.org/10.1093/jac/dkz210

Published: 18 May 2019

 

Abstract

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.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; E. Coli; Ciprofloxacin; Fluoroquinolones; N-Acetylcysteine.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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