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A biofilm is a structured community of microorganisms, such as bacteria or fungi, embedded within a self-produced matrix of extracellular polymeric substances (EPS) consisting of polysaccharides, proteins, lipids, and extracellular DNA. This matrix acts as a protective 3D scaffold that shields the microbes from environmental stressors, host immune defenses, and antimicrobial treatments, often increasing antibiotic tolerance by up to 1,000-fold compared to free-floating planktonic cells. Biofilms are a primary driver of chronic and recalcitrant infections, particularly in conditions like cystic fibrosis, chronic wounds, and infections associated with indwelling medical devices such as catheters and prosthetic joints. Therapeutic intervention typically involves a multi-targeted approach aimed at disrupting the EPS matrix, inhibiting cell-to-cell communication (quorum sensing), and enhancing the penetration of antibiotics to eradicate dormant persister cells. Despite their clinical significance, biofilms remain a major therapeutic challenge due to their complex, often multi-species composition and their inherent resistance to conventional monotherapies.
Drugs targeting the biofilm matrix work by degrading extracellular DNA (eDNA) to reduce structural integrity, enzymatically hydrolyzing exopolysaccharides (e.g., using glycoside hydrolases), inhibiting quorum sensing pathways to prevent maturation, or utilizing chelating agents to disrupt the ionic cross-linking of the matrix. These actions facilitate the penetration of traditional antibiotics to reach and kill the embedded microorganisms, including metabolically dormant persister cells.
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