Reactive oxygen species accelerate acquisition of antibiotic resistance in .

iScience

Laboratory for Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.

Published: December 2023

Reactive oxygen species (ROS) produced as a secondary effect of bactericidal antibiotics are hypothesized to play a role in killing bacteria. If correct, ROS may play a role in development of resistance. Here we report that single-gene knockout strains with reduced ROS scavenging exhibited enhanced ROS accumulation and more rapid acquisition of resistance when exposed to sublethal levels of bactericidal antibiotics. Consistent with this observation, the ROS scavenger thiourea in the medium decelerated resistance development. Thiourea downregulated the transcriptional level of error-prone DNA polymerase and DNA glycosylase MutM, which counters the incorporation and accumulation of 8-hydroxy-2'-deoxyguanosine (8-HOdG) in the genome. The level of 8-HOdG significantly increased following incubation with bactericidal antibiotics but decreased after treatment with the ROS scavenger thiourea. These observations suggest that in sublethal levels of ROS stimulate development of resistance, providing a mechanistic basis for hormetic responses induced by antibiotics.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679899PMC
http://dx.doi.org/10.1016/j.isci.2023.108373DOI Listing

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