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The mucin and bacterial biofilm matrix is a complex, heterogeneous structural barrier composed of host-derived mucin glycoproteins and microbially-produced extracellular polymeric substances (EPS) [1, 3]. These EPS components typically include polysaccharides, proteins, and extracellular DNA (eDNA) that provide a scaffold for bacterial communities to thrive [3]. In chronic infections, such as those found in cystic fibrosis or chronic wounds, bacteria utilize this matrix to evade the host immune system and resist antibiotic penetration [1]. The interaction between host mucins and bacterial products increases the viscoelasticity of the environment, impairing natural clearance mechanisms like mucociliary transport [2]. Therapeutic targeting of this matrix involves the use of mucolytics to break disulfide bonds and nucleases to degrade eDNA, thereby thinning the matrix and facilitating clearance [2, 4]. Emerging treatments also focus on glycoside hydrolases that specifically target the bacterial exopolysaccharides within the biofilm to destabilize the structure [3]. By disrupting this physical barrier, these therapies aim to restore the efficacy of conventional antibiotics and improve patient outcomes in chronic inflammatory and infectious diseases [1, 2].
Disruption of disulfide bonds in mucin glycoproteins, enzymatic degradation of extracellular DNA (eDNA), and hydrolysis of bacterial exopolysaccharides to reduce matrix viscosity and enhance antibiotic penetration [2, 3].
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