Abstract

Significance Substantial knowledge exists about how antibiotics interfere with core bacterial processes by binding to specific targets. Recently it has become appreciated that blocking these functions alters cellular redox state, and these perturbations may contribute to the lethality of antibiotics. In this work we explore whether antibiotic treatment of bacteria affects cellular oxidative stress and the role of such stress in antibiotic-mediated killing. We find that antibiotics dynamically alter cellular respiration and induce lethal levels of intracellular hydrogen peroxide. Antioxidants, including oxidative stress defense proteins, significantly reduce the killing by antibiotics, which is highly sensitive to the presence of molecular oxygen. These findings underscore the complex nature of antibiotic action and suggest practical approaches to enhancing our current antibiotic arsenal.