Disulfide bonds in mucin and bacterial biofilm extracellular matrix

Disulfide bonds are critical covalent linkages that stabilize the three-dimensional structure of mucin glycoproteins and the extracellular polymeric substances (EPS) of bacterial biofilms (Thornton et al., 2008, PubMed). In the respiratory tract, these bonds cross-link mucin monomers into a dense, viscoelastic gel that traps pathogens; however, in diseases like cystic fibrosis and chronic obstructive pulmonary disease (COPD), excessive cross-linking leads to pathologically thick mucus (Fahy & Dickey, 2010, NEJM). Similarly, disulfide bonds within the biofilm matrix contribute to the structural integrity and antibiotic resistance of bacterial communities by anchoring proteins and polysaccharides (Zhao & Liu, 2010, PubMed). Therapeutic intervention typically involves thiol-containing reducing agents, such as N-acetylcysteine (NAC), which break these bonds through thiol-disulfide exchange (StatPearls, 2023). This process reduces the viscosity of mucus, facilitating mucociliary clearance, and destabilizes biofilms to enhance the penetration and efficacy of co-administered antibiotics (Olofsson et al., 2003, Applied and Environmental Microbiology). Targeting these chemical bonds remains a cornerstone strategy for managing obstructive airway diseases and persistent microbial infections.

Other names

Mucin disulfide cross-linksBiofilm matrix disulfide bondsThiol-disulfide exchange targetsMucus disulfide bonds

Thiol-disulfide exchange reaction resulting in the reduction of covalent disulfide cross-links into free sulfhydryl groups, causing depolymerization of the macromolecular matrix (StatPearls, 2023).