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The bacterial biofilm extracellular polymeric substance (EPS) cross-linking network is a complex, self-produced three-dimensional matrix composed of exopolysaccharides, proteins, lipids, and extracellular DNA (eDNA) that encases microbial communities (Flemming & Wingender, 2010). This network serves as the structural scaffold that holds biofilms together, providing mechanical stability and acting as a protective barrier against environmental stressors, host immune cells, and antimicrobial penetration (Ciofu et al., 2022). Cross-linking within the EPS is facilitated by physical entanglements, hydrophobic interactions, and ionic bridges mediated by multivalent cations such as calcium, magnesium, and iron (Karygianni et al., 2020). In clinical settings, this network is a major driver of antibiotic tolerance and chronic infection persistence in conditions like cystic fibrosis, chronic wounds, and medical device-related infections (Tetz et al., 2009). Therapeutic targeting of the EPS cross-linking network involves the use of matrix-degrading enzymes or chelating agents to disrupt the structural scaffold, thereby dispersing the biofilm and restoring the efficacy of conventional antibiotics (Karygianni et al., 2020).
Disruption of the structural integrity of the biofilm matrix through enzymatic cleavage of polymers such as extracellular DNA and exopolysaccharides, or through the chelation of multivalent cations that stabilize the cross-linking network (Flemming & Wingender, 2010; Karygianni et al., 2020).
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