Disulfide bonds in mucins and biofilm extracellular polymeric substances

Disulfide bonds are critical covalent cross-links that stabilize the three-dimensional architecture of mucin glycoproteins and the extracellular polymeric substances (EPS) of bacterial biofilms. In mucins, these bonds link cysteine-rich domains of monomeric subunits to form massive, viscoelastic polymers that constitute the primary structural framework of mucus (PubMed: 24951272). In biofilms, disulfide bonds contribute to the stability of the proteinaceous matrix, protecting bacterial colonies from host immune responses and antibiotic penetration (PubMed: 30254116). Therapeutically, these bonds are targeted by mucolytic agents, such as N-acetylcysteine, which utilize free thiol groups to reduce the disulfide bridges into individual sulfhydryl groups (StatPearls: NBK537183). This chemical reduction breaks down the high-molecular-weight polymers, significantly decreasing the viscosity of pathological mucus and destabilizing the biofilm matrix. This approach is vital in treating respiratory conditions like cystic fibrosis and COPD, as well as in disrupting persistent bacterial infections.

Other names

Mucin disulfide bridgesEPS disulfide cross-linksCystine linkagesDisulfide cross-links

Reduction of disulfide bonds via thiol-disulfide exchange, leading to the cleavage of high-molecular-weight mucin polymers and biofilm matrix proteins into smaller, less viscous subunits.