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The biofilm extracellular polymeric substance (EPS) matrix is a complex, self-produced scaffold composed of polysaccharides, proteins, lipids, and extracellular DNA (eDNA) that encases microbial communities. Calcium ions (Ca2+) play a critical role in this architecture by forming ionic bridges between negatively charged polymers, such as alginate or eDNA, which significantly enhances the mechanical stability and chemical resistance of the biofilm (PMID: 28913362, PMID: 30143604). This matrix acts as a physical and chemical barrier that protects bacteria from host immune cells and limits the penetration of traditional antibiotics, contributing to the persistence of chronic infections in conditions like cystic fibrosis and medical device colonization (PMID: 23632386). Therapeutic strategies targeting the EPS matrix involve the use of chelating agents to disrupt calcium bridges or enzymes like DNase and glycoside hydrolases to degrade the structural polymers (PMID: 33033258). By destabilizing the matrix, these interventions promote biofilm dispersal and restore the efficacy of co-administered antimicrobial agents (PMID: 25239654).
Drugs targeting the EPS matrix and calcium bridges work by sequestering divalent cations (like Ca2+ and Mg2+) to destabilize the structural network, enzymatically degrading matrix components such as eDNA or polysaccharides, or inhibiting the synthesis of matrix polymers to promote biofilm dispersal and increase the penetration of conventional antibiotics.
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