Disulfide bonds of mucin glycoproteins and biofilm extracellular polymeric substances

Disulfide bonds are critical covalent cross-links that maintain the three-dimensional architecture and viscoelastic properties of both human mucus and bacterial biofilms [NIH, 2025]. In the human respiratory and gastrointestinal tracts, gel-forming mucins such as MUC5AC and MUC5B polymerize via disulfide bridges between cysteine-rich domains, creating a dense network that traps pathogens but can become pathologically thick in respiratory diseases like cystic fibrosis and COPD [ScienceDaily, 2015; Dovepress, 2024]. Similarly, in bacterial biofilms, disulfide bonds stabilize the protein components of the extracellular polymeric substance (EPS) matrix, contributing to antibiotic resistance and environmental resilience [NIH, 2017]. Targeting these bonds with reducing agents, such as N-acetylcysteine or novel thiol-saccharides like MUC-031, facilitates the breakdown of these macro-structures by converting disulfide bridges into free sulfhydryl groups [NIH, 2023; ResearchGate, 2020]. This process, known as mucolysis or biofilm disruption, reduces the viscosity of secretions and enhances the penetration of antibiotics and immune cells [bioRxiv, 2019]. Consequently, these bonds represent a key therapeutic target for managing muco-obstructive lung diseases and chronic biofilm-associated infections [NIH, 2019].

Other names

Mucus disulfide bridgesBiofilm matrix disulfide bondsThiol-disulfide exchange targetsMucin cross-linksExtracellular polymeric substance disulfide bonds

Thiol-disulfide exchange reaction; reduction of intermolecular disulfide bonds to free thiols, resulting in the depolymerization of mucin polymers and extracellular polymeric substance (EPS) proteins, thereby reducing the viscosity and structural stability of the matrix.