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Calcium-bridged extracellular DNA (eDNA) and extracellular polymeric substance (EPS) structures are critical components of the biofilm matrix that provide structural stability and protection to microbial communities [Whitchurch et al., 2002; Science]. In many pathogenic biofilms, such as those formed by Pseudomonas aeruginosa, negatively charged eDNA and polysaccharides are cross-linked by divalent calcium ions (Ca²⁺), creating a robust physical barrier [Mulcahy et al., 2008; PLOS Pathogens]. This matrix protects bacteria from environmental stressors and host immune cells, while significantly limiting the penetration of antimicrobial agents, contributing to high levels of antibiotic tolerance [Das et al., 2014; Soft Matter]. Targeting these bridges through the use of chelating agents like EDTA or enzymes like DNase I (Dornase alfa) can destabilize the biofilm architecture, making the embedded bacteria more susceptible to treatment [Kiedrowski et al., 2011; Applied and Environmental Microbiology]. This approach is particularly relevant in treating chronic infections associated with cystic fibrosis, chronic wounds, and medical device colonization [NIH, 2023]. By disrupting the ionic interactions that hold the matrix together, these therapies aim to facilitate biofilm clearance and improve clinical outcomes [PubMed, 2022].
Disruption of the biofilm matrix through the chelation of divalent calcium ions (which serve as ionic bridges) or the enzymatic degradation of the eDNA and EPS components, leading to the loss of structural integrity and increased penetration of antimicrobial agents.
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