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DNA–Calcium–DNA bridges are essential structural motifs within the extracellular polymeric substance (EPS) that constitutes the matrix of bacterial biofilms (Whitchurch et al., 2002). These bridges are formed through the electrostatic interaction between negatively charged extracellular DNA (eDNA) and divalent calcium ions (Ca²⁺), which act as cross-linking agents to provide mechanical strength and viscoelasticity to the biofilm (Das et al., 2014). This structural framework serves as a physical barrier that protects pathogenic bacteria from the host's immune system and significantly reduces the penetration of antibiotics, contributing to the persistence of chronic infections (Gloag et al., 2013). Clinically, these bridges are highly relevant in conditions such as Pseudomonas aeruginosa infections in cystic fibrosis and medical device-related biofilms (Mulcahy et al., 2008). Therapeutic strategies target these bridges by using DNA-degrading enzymes like Dornase alfa to cleave the DNA backbone or calcium-chelating agents like EDTA to sequester the ions, thereby liquefying the matrix and enhancing the efficacy of co-administered antimicrobial agents (Jones et al., 2013).
Chelation of divalent calcium ions to destabilize electrostatic cross-links and enzymatic hydrolysis of extracellular DNA to degrade the structural scaffold of the biofilm matrix.
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