Indirect reactive oxygen species-mediated damage to bacterial DNA and other cellular components (ROS-mediated bacterial damage)

Indirect reactive oxygen species (ROS)-mediated damage refers to a proposed common mechanism of bacterial lethality induced by various classes of bactericidal antibiotics (Kohanski et al., 2007, Cell). According to this model, the primary interaction between an antibiotic and its specific target, such as the ribosome or DNA gyrase, triggers a downstream metabolic cascade involving the tricarboxylic acid (TCA) cycle and the electron transport chain. This leads to the destabilization of iron-sulfur clusters and the release of free iron, which then fuels the Fenton reaction to produce highly reactive hydroxyl radicals (Dwyer et al., 2014, PNAS). These radicals cause extensive, non-specific damage to bacterial DNA, proteins, and lipids, contributing significantly to the drug's killing efficacy. Although the universality of this mechanism has been debated (Liu & Imlay, 2013, Science), it remains a key area of research for enhancing antibiotic activity through the use of redox-active adjuvants. Targeting the bacterial response to oxidative stress is a potential strategy to combat antibiotic resistance in various infectious diseases.

Other names

Oxidative stress-induced bacterial lethalityAntibiotic-induced ROS productionSecondary oxidative damageHydroxyl radical-mediated damage

Bactericidal antibiotics trigger metabolic perturbations that lead to the depletion of NADH, disruption of iron-sulfur clusters, and the subsequent generation of hydroxyl radicals via the Fenton reaction, which causes lethal damage to cellular macromolecules.