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Bacterial and fungal cell membranes are essential lipid bilayers that maintain cellular homeostasis and protect against environmental stress (Heidary et al., 2022, Frontiers in Microbiology). In bacteria, the membrane is a site for energy transduction and lipid synthesis, while fungal membranes are characterized by the presence of ergosterol, a primary target for polyene antifungals like Amphotericin B (Anderson et al., 2014, Nature Chemical Biology). Biofilms represent a higher-order structural organization where microbes are encased in a self-produced extracellular polymeric substance (EPS) matrix, which significantly limits the penetration of antimicrobial agents and protects the community from host immune clearance (Flemming & Wingender, 2010, Nature Reviews Microbiology). Therapeutic targeting of these structures involves physical disruption, such as the pore-forming mechanism of polymyxins in Gram-negative bacteria or the sequestration of ergosterol in fungi. Biofilm-specific strategies focus on degrading the EPS matrix or inhibiting quorum sensing to transition the microbes back to a more susceptible planktonic state (Roy et al., 2018, Virulence).
Disruption of membrane integrity, pore formation, depolarization of the membrane potential, and degradation of the extracellular polymeric substance (EPS) matrix.
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