Disulfide bonds and reactive oxygen species

Disulfide bonds are essential covalent cross-links that stabilize the gel-forming mucin polymers, such as MUC5AC and MUC5B, which constitute the primary framework of human mucus [1][3]. In the context of bacterial infections, similar disulfide bridges within the extracellular polymeric substances (EPS) contribute to the structural integrity and resilience of biofilms, protecting bacteria from host immune responses and antibiotic penetration [4]. Reactive oxygen species (ROS) are byproduct molecules of oxygen metabolism that, when produced in excess during chronic inflammation, lead to oxidative stress and further promote mucus hypersecretion and tissue damage [2]. Therapeutic intervention targeting these components typically involves mucolytic agents like N-acetylcysteine, which possess free sulfhydryl groups capable of reducing disulfide bonds to sulfhydryl groups through thiol-disulfide exchange [1]. This process effectively lowers the viscosity of pathological mucus and disrupts the biofilm matrix, facilitating clearance and enhancing the efficacy of co-administered antibiotics [1][4]. Furthermore, these agents act as antioxidants by directly neutralizing ROS or providing cysteine for the synthesis of glutathione, thereby protecting cells from oxidative injury in respiratory diseases like COPD and cystic fibrosis [2].

Other names

Disulfide bonds in mucus and bacterial biofilm extracellular matrix components; reactive oxygen speciesMucin disulfide bridgesBiofilm extracellular polymeric substance (EPS) disulfide bondsReactive oxygen speciesROSOxidative stress components

Reduction of disulfide bonds via thiol-disulfide exchange and direct/indirect neutralization of reactive oxygen species.