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Bacterial cellular redox systems and reactive oxygen species (ROS) pathways are complex biochemical networks that maintain the intracellular reduction-oxidation balance and protect the cell from oxidative damage (Imlay, 2013). These systems comprise various enzymes, including superoxide dismutases (SOD), catalases, and peroxidases, alongside low-molecular-weight thiols like glutathione and the thioredoxin/glutaredoxin systems (Ezraty et al., 2017). These pathways are vital for bacterial survival during infection, as they counteract the oxidative burst produced by host phagocytes (Memar et al., 2018). In the context of antimicrobial therapy, these systems are considered significant targets because many bactericidal antibiotics are hypothesized to kill bacteria by inducing a common oxidative stress response that generates lethal hydroxyl radicals (Kohanski et al., 2007). By inhibiting these protective redox systems or actively promoting ROS accumulation, therapeutic agents can potentiate the activity of existing antibiotics and help overcome mechanisms of multi-drug resistance. However, the development of such therapies must carefully account for potential off-target effects on host mitochondrial redox homeostasis and the ability of bacteria to rapidly adapt through the upregulation of alternative antioxidant defenses.
Inhibition of antioxidant enzymes, disruption of iron-sulfur clusters, and stimulation of the Fenton reaction to generate lethal hydroxyl radicals.
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