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Bacterial and fungal cell membranes, along with the biofilm extracellular matrix (ECM), represent the fundamental protective barriers of microbial pathogens. The cell membrane is a lipid bilayer that maintains cellular homeostasis and serves as a scaffold for transport proteins, making it a primary target for membrane-active antibiotics and antifungals (StatPearls, 2023; NCBI Bookshelf, 2022). The biofilm ECM is a self-produced scaffold of extracellular polymeric substances (EPS), including polysaccharides and extracellular DNA, which shields microbial communities from host immunity and limits antibiotic penetration (Nature Reviews Microbiology, 2016). These structures are central to the development of chronic infections and antimicrobial resistance, as they provide both physical and chemical defense mechanisms. Therapeutic interventions targeting these components aim to either directly lyse the microbial cell or degrade the biofilm matrix to enhance the efficacy of co-administered drugs. However, the clinical utility of such agents is often constrained by toxicity to host tissues and the rapid evolution of microbial resistance (Frontiers in Microbiology, 2020; PubMed, 2021).
Mechanisms include the disruption of lipid bilayer integrity through pore formation (e.g., polymyxins, polyenes), inhibition of essential membrane components like ergosterol (e.g., azoles), and the enzymatic degradation of extracellular polymeric substances (EPS) such as eDNA to destabilize biofilm architecture (PubChem, 2024; StatPearls, 2023; Nature Reviews Microbiology, 2016).
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