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Microbial reactive oxygen species (ROS) generation pathways refer to the collective metabolic and enzymatic processes that result in the production of highly reactive oxygen-containing molecules, such as superoxide (O2•−), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH), within microbial cells [1.2.1, 1.2.3]. The primary endogenous sources of ROS in microbes include the respiratory electron transport chain, where electrons leak to oxygen, and the autoxidation of flavoproteins [1.1.3, 1.2.1]. These pathways are critical in the mechanism of action for several classes of bactericidal antibiotics, which are thought to induce a common oxidative stress response leading to cellular death through damage to DNA, proteins, and membrane lipids [1.1.2, 1.2.1]. Additionally, novel antimicrobial strategies, including photodynamic therapy and the use of metal-based nanoparticles, specifically aim to overwhelm microbial antioxidant defenses by stimulating these ROS generation pathways [1.1.4, 1.2.3]. Despite their therapeutic potential, the non-specific nature of ROS poses challenges regarding host tissue toxicity and the potential for inducing mutations that could lead to antibiotic resistance [1.1.2, 1.2.3]. Furthermore, the efficacy of ROS-inducing therapies can be limited by the microbial ability to remodel metabolism, such as upregulating the glyoxylate shunt to reduce endogenous ROS formation [1.1.1, 1.1.2].
Induction of endogenous ROS production, inhibition of antioxidant enzymes, and activation of the Fenton reaction to generate lethal hydroxyl radicals.
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