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Metal ions, particularly divalent and trivalent cations like calcium (Ca2+), magnesium (Mg2+), and iron (Fe3+), serve as critical structural scaffolds within the extracellular polymeric substance (EPS) matrix of microbial biofilms. These ions facilitate the cross-linking of negatively charged EPS components, such as extracellular DNA (eDNA), proteins, and polysaccharides, thereby providing mechanical stability and protection against chemical and physical stressors (Mulcahy et al., 2008, Journal of Bacteriology). In clinical settings, these ions contribute to the persistence of chronic infections by maintaining the biofilm's integrity, which acts as a barrier to both the host immune system and conventional antibiotics (Banin et al., 2005, PNAS). Therapeutic targeting of these metal ions primarily involves the use of chelating agents that sequester the ions, effectively dissolving the molecular glue of the biofilm (Percival et al., 2005, Journal of Wound Care). This process promotes biofilm dispersal and significantly increases the susceptibility of the resident bacteria to antimicrobial treatments, making it a promising strategy for managing recalcitrant infections in cystic fibrosis, chronic wounds, and on medical implants (Ganeshnarayan et al., 2009, Molecular Oral Microbiology).
Sequestration of divalent and trivalent cations (e.g., Ca2+, Mg2+, Fe3+) to disrupt electrostatic cross-linking of extracellular polymeric substances, leading to biofilm destabilization, increased porosity, and enhanced antibiotic penetration.
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