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Microbial biomolecules (targeted by reactive nitrogen oxide species) represent a broad class of cellular components, including proteins, DNA, and lipids, that are susceptible to chemical modification by reactive nitrogen oxide species (RNOS) (Encyclopedia Pub, 2022). RNOS such as nitric oxide (NO), peroxynitrite (ONOO-), and nitrogen dioxide (NO2) are produced by the host immune system (e.g., via inducible nitric oxide synthase) to neutralize invading pathogens (NIH, 2019). These species exert antimicrobial effects through mechanisms such as the S-nitrosylation of critical cysteine thiols, the disruption of iron-sulfur (Fe-S) clusters in metabolic enzymes like aconitase, and the deamination of DNA bases (NIH, 2024; NIH, 2021). Therapeutic approaches targeting these biomolecules involve the use of nitric oxide donors, acidified nitrite, and NO-releasing materials to induce lethal nitrosative stress in microbes (NIH, 2019; NIH, 2024). While effective against a wide range of bacteria, fungi, and parasites, the non-specific reactivity of RNOS poses challenges regarding host toxicity and systemic side effects like hypotension (NIH, 2024; Semanticscholar, 2021).
Induction of nitrosative stress through S-nitrosylation of thiols, nitration of tyrosine residues, disruption of iron-sulfur (Fe-S) clusters, and DNA deamination.
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