This study showed that inducing microbial reactive oxygen species (ROS) can potentiate antibiotic activity. The authors used a systems biology approach to identify ROS-generating reactions in Escherichia coli metabolism, then experimentally tested deletions of genes that encode these metabolic enzymes. Deletion of either of four target genes (cyoA, nuoG, sdhC or pta) increased the sensitivity to β-lactam and/or fluoroquinolone antibiotics. Moreover, chemical inhibition of one target — succinate dehydrogenase — increased the sensitivity to oxidant and ampicillin treatment.