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Bacterial cellular components susceptible to reactive oxygen species (ROS) encompass a diverse array of vital molecules including DNA, proteins, and membrane lipids that undergo oxidative damage during stress. ROS such as superoxide, hydrogen peroxide, and the highly reactive hydroxyl radical target specific chemical moieties within the cell. For instance, hydroxyl radicals cause lethal double-strand breaks and base modifications in the bacterial genome (Imlay, J. A., 2013, Annual Review of Microbiology). Proteins containing solvent-exposed iron-sulfur [4Fe-4S] clusters, such as dehydratases, are particularly vulnerable, leading to the release of iron and subsequent Fenton chemistry (Imlay, J. A., 2003, Annual Review of Microbiology). Additionally, ROS can induce lipid peroxidation, compromising the structural integrity of the bacterial cell membrane and disrupting the proton motive force (Ezraty, B., et al., 2017, Nature Reviews Microbiology). While many bactericidal antibiotics like aminoglycosides and fluoroquinolones are thought to stimulate ROS production as a secondary mechanism of lethality, this remains a subject of scientific debate (Kohanski, M. A., et al., 2007, Cell). Because this term describes a broad range of molecular vulnerabilities rather than a single protein or receptor, it is generally categorized as a collective mechanism of action for antimicrobial agents rather than a specific therapeutic target.
Induction of macromolecular oxidative damage via Fenton chemistry and radical formation, leading to loss of cellular integrity and death.
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