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Polymeric extracellular matrices (PEMs) are complex, three-dimensional networks of macromolecules, primarily composed of polysaccharides, proteins, and extracellular DNA (eDNA), that form the structural backbone of mucus and microbial biofilms (Flemming et al., 2016, Nature Reviews Microbiology). In the human body, mucus PEMs act as a critical physical and chemical barrier that protects epithelial surfaces from dehydration, mechanical stress, and pathogens (Fahy and Dickey, 2010, NEJM). In the context of infection, microorganisms secrete their own PEMs, known as extracellular polymeric substances (EPS), to create a protective niche that shields them from antibiotics and the host immune system (Hall-Stoodley et al., 2004, Nature Reviews Microbiology). Pathological accumulation or altered rheology of these matrices is central to the pathogenesis of diseases like cystic fibrosis, where hyper-viscous mucus leads to airway obstruction and chronic infection (Pressler, 2008, Paediatric Respiratory Reviews). Therapeutic targeting of PEMs aims to disrupt the structural integrity of these networks to improve clearance or enhance the penetration of co-administered antimicrobial agents. Common pharmacological approaches include the use of mucolytics like N-acetylcysteine, which reduces disulfide bonds in mucins, and enzymes like Dornase alfa, which degrades eDNA (Boucher, 2007, Journal of Internal Medicine).
Enzymatic cleavage of structural polymers (e.g., DNA by nucleases, polysaccharides by glycoside hydrolases), chemical reduction of cross-linking disulfide bonds in glycoproteins, and chelation of divalent cations (like Ca2+ and Mg2+) that stabilize the matrix architecture.
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