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Divalent cations, primarily calcium (Ca2+) and magnesium (Mg2+), are essential structural components of microbial cell walls and the extracellular matrix of biofilms (Nikaido, 2003, Microbiology and Molecular Biology Reviews). In Gram-negative bacteria, these ions provide stability to the outer membrane by cross-linking the negatively charged phosphate groups of lipopolysaccharide (LPS) molecules. Within the biofilm environment, divalent cations act as ionic bridges between extracellular polymeric substances (EPS), such as alginate and extracellular DNA, which maintains the mechanical integrity of the microbial community (Whitchurch et al., 2002, Science). Depletion of these ions through the use of chelating agents like EDTA or citrate leads to the destabilization of the cell wall and the dissolution of the biofilm matrix (Banin et al., 2006). This disruption increases the permeability of the bacterial membrane and enhances the penetration of conventional antibiotics, making it a valuable strategy for treating recalcitrant infections (Mulcahy et al., 2008, Journal of Medical Microbiology). Consequently, targeting divalent cations is a recognized approach in managing biofilm-associated conditions, including cystic fibrosis and catheter-related bloodstream infections (Percival et al., 2005, Journal of Hospital Infection). Therapeutic applications often involve using chelators as adjuncts to standard antimicrobial therapy to overcome phenotypic resistance.
Chelation of divalent cations (primarily Ca2+ and Mg2+) disrupts the ionic bridges that stabilize the lipopolysaccharide (LPS) layer of Gram-negative bacteria and the extracellular polymeric substance (EPS) matrix of biofilms, leading to increased membrane permeability and biofilm dissolution (Banin et al., 2006, Applied and Environmental Microbiology).
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