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The microbial biofilm extracellular matrix (ECM) is a complex, self-produced architectural scaffold composed of extracellular polymeric substances (EPS), including polysaccharides, proteins, lipids, and extracellular DNA (eDNA) (Flemming & Wingender, 2010). It serves as the primary structural element of biofilms, providing mechanical stability and facilitating adhesion to both biotic and abiotic surfaces (Koo et al., 2017). Beyond structure, the ECM acts as a robust physical and chemical barrier that protects encased microorganisms from host immune cells and limits the penetration of antimicrobial agents, contributing to high levels of antibiotic tolerance (Ciofu et al., 2022). In clinical contexts, the ECM is central to the persistence of chronic infections, such as those found in cystic fibrosis lungs, chronic wounds, and on medical implants like catheters and heart valves (Karygianni et al., 2020). Therapeutic interventions targeting the ECM, such as the use of Dornase alfa to degrade eDNA or various glycoside hydrolases to break down polysaccharides, aim to destabilize the biofilm architecture (Tetz et al., 2009). By disrupting this protective shield, these treatments enhance the efficacy of co-administered antibiotics and facilitate the clearance of pathogens by the host immune system (Yan & Bassler, 2019).
Enzymatic degradation of extracellular polymeric substances (e.g., eDNA, polysaccharides), chelation of divalent cations (Ca2+, Mg2+) that stabilize the matrix, and inhibition of matrix component synthesis to enhance antibiotic penetration and immune clearance.
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