Effect of N-acetyl-cysteine on antibiotic mediated bacterial mutagenesis

Abstract

Bactericidal antibiotics increase bacterial mutagenesis mediated by induction of the SOS response and production of Reactive Oxygen Species (ROS) promoting the emergence of antibiotic resistance variants. Interestingly, high levels of ROS can additionally induce SOS. Therefore, antibiotics may produce cumulative mutagenic effect (ROS plus SOS), although the relative contribution of each factor has not been yet clarified. Inhibition of SOS and/or ROS could be useful strategies to diminish the mutagenic effect of antibiotics. Among other molecules, antioxidants have been suggested as possible adjuvants in antibiotic therapy. Nonetheless, ROS production has been linked to lethality of bactericidal antibiotics in bacteria. Thus, antioxidants could have an antagonistic effect on this lethality. Our research is aimed at investigating i) whether antioxidants can affect the killing activity of antibiotics, and ii) the relative contribution of SOS and ROS in bacterial mutagenesis. N-Acetyl-Cysteine, a widely used FDA approved antioxidant, was able to decrease the mutagenesis promoted by ciprofloxacin, a bactericidal antibiotic and well-known SOS inducer without affecting viability of Escherichia coli. The relative contribution of ROS and SOS on mutagenesis will also be presented.