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The microbial cell surface and biofilm matrix constitute the primary physical interface between microorganisms and their environment, serving as a critical defense mechanism against host immunity and antimicrobial agents (Flemming & Wingender, 2010, Nature Reviews Microbiology). The cell surface consists of the plasma membrane and, in many species, a rigid cell wall that maintains structural integrity and regulates molecular transport (Silhavy et al., 2010, Cold Spring Harbor Perspectives in Biology). Surrounding this, the biofilm matrix is a complex assembly of extracellular polymeric substances (EPS), including polysaccharides, proteins, and extracellular DNA, which facilitates stable adhesion and provides a protective shield for microbial communities (Koo et al., 2017, Nature Reviews Microbiology). These structures are central to the pathogenesis of chronic infections, as they contribute significantly to the phenomenon of antimicrobial tolerance by physically hindering drug penetration and harboring persistent cells. Therapeutic interventions often target specific components, such as peptidoglycan synthesis in the cell wall or the enzymatic breakdown of matrix EPS to sensitize bacteria to conventional antibiotics (Donlan, 2002, Emerging Infectious Diseases). Consequently, this composite target is a focal point for developing next-generation anti-infectives aimed at treating recalcitrant biofilm-mediated diseases.
Drugs targeting these structures act by disrupting the physical integrity of the cell membrane, inhibiting the biosynthesis of cell wall components like peptidoglycan or beta-glucan, or enzymatically degrading the extracellular polymeric substances that hold the biofilm together (Koo et al., 2017, Nature Reviews Microbiology).
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