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Metal ions in microbial biofilms, including calcium, magnesium, iron, and zinc, serve as essential structural and functional components of the biofilm architecture. These ions facilitate the cross-linking of negatively charged extracellular polymeric substances (EPS), such as polysaccharides and extracellular DNA, which provides the biofilm with mechanical stability and resistance to environmental stressors (PMID: 28943321). Beyond their structural role, metal ions act as vital cofactors for microbial enzymes and are central to signaling pathways that regulate biofilm maturation and virulence (PMID: 30244113). In clinical settings, the sequestration of these ions by the biofilm matrix contributes significantly to the recalcitrance of chronic infections and the failure of standard antibiotic therapies. Therapeutic targeting of these ions typically involves the use of chelating agents like EDTA or iron-sequestering molecules like lactoferrin to disrupt the EPS matrix (PMID: 21859875). This disruption facilitates the dispersal of the microbial community and restores the efficacy of the host immune response and traditional antimicrobial agents.
Chelation of divalent and trivalent cations (such as Ca2+, Mg2+, and Fe3+) destabilizes the extracellular polymeric substance (EPS) matrix by disrupting electrostatic cross-links. This increases biofilm permeability, promotes biofilm dispersal, and enhances the penetration and efficacy of co-administered conventional antibiotics.
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