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Calcium and magnesium ions are critical structural components of microbial biofilms, where they serve to cross-link negatively charged extracellular polymeric substances (EPS) such as polysaccharides, proteins, and extracellular DNA (Sarkisova et al., 2005; Mulcahy et al., 2008). This ionic bridging provides mechanical stability and integrity to the biofilm matrix, protecting the embedded microbial community from environmental stressors and the host immune system. In clinical settings, these ions are targeted by chelating agents like EDTA or citrate to destabilize the biofilm architecture (Banin et al., 2006). By sequestering these divalent cations, the EPS matrix is weakened, which facilitates the detachment of the biofilm and significantly enhances the efficacy of co-administered antibiotics. This strategy is particularly relevant in treating chronic infections associated with medical devices, cystic fibrosis, and non-healing wounds where biofilm-mediated resistance is a major challenge. While effective as a localized treatment, systemic use of chelators targeting these ions must be carefully managed to avoid disrupting host calcium and magnesium homeostasis.
Chelation of divalent cations (Ca2+ and Mg2+) disrupts the ionic bridges that stabilize the extracellular polymeric substance (EPS) matrix, leading to biofilm dissolution and increased penetration of antimicrobial agents.
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