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The bacterial outer membrane and the biofilm matrix are critical structural components that provide a protective environment for bacteria, particularly Gram-negative pathogens (Silhavy et al., 2010). The outer membrane is an asymmetric lipid bilayer rich in lipopolysaccharides (LPS), while the biofilm matrix is a complex assembly of extracellular polymeric substances (EPS) including polysaccharides, proteins, and extracellular DNA (eDNA) (Flemming & Wingender, 2010). These structures are stabilized by divalent cations, such as calcium and magnesium, which cross-link negatively charged molecules to maintain structural rigidity (Mulcahy et al., 2008). In clinical settings, these components act as a formidable barrier against the host immune system and significantly reduce the penetration of many antibiotics, contributing to chronic and recalcitrant infections (Hall-Stoodley et al., 2004). Therapeutic interventions target these structures through various mechanisms: polymyxins bind to LPS to disrupt membrane integrity, while chelating agents like EDTA sequester the stabilizing cations to destabilize the biofilm matrix and increase permeability (Vaara, 1992; Lambert et al., 2001). This target complex is essential for bacterial survival under stress and represents a major hurdle in treating persistent infections.
Disruption of the bacterial outer membrane through competitive displacement of divalent cations from lipopolysaccharides (LPS) by polycationic antibiotics; chelation of divalent cations (Ca2+, Mg2+) to destabilize the extracellular polymeric substance (EPS) matrix of biofilms; and enzymatic degradation of matrix components such as eDNA and polysaccharides.
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