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Bacterial biofilm extracellular polymeric substance (EPS) is a complex, self-produced matrix that encases microbial communities, providing structural integrity and protection against environmental stressors. It is composed primarily of exopolysaccharides, extracellular DNA (eDNA), proteins, and lipids, which together form a robust three-dimensional scaffold. The EPS acts as a physical and chemical barrier that significantly limits the penetration of antibiotics and host immune cells, contributing to the high level of antimicrobial tolerance observed in biofilms. In clinical settings, EPS-mediated biofilms are central to the persistence of chronic infections, such as those found in cystic fibrosis lungs, chronic wounds, and on indwelling medical devices. Therapeutic strategies targeting the EPS aim to degrade its components—using enzymes like DNases and glycoside hydrolases—or disrupt its stabilizing ionic bonds through chelation. By breaking down this protective scaffold, these biofilm-disrupting agents can restore the susceptibility of the embedded bacteria to conventional antimicrobial treatments and facilitate their clearance by the immune system. However, a significant challenge in targeting the EPS is the risk of releasing viable bacteria into the bloodstream, potentially leading to systemic dissemination or sepsis.
Enzymatic degradation of matrix polymers such as extracellular DNA and polysaccharides, chelation of divalent cations that stabilize the matrix, and physical disruption of the matrix to enhance antibiotic penetration and immune access.
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