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Microbial cells and biofilm matrices constitute a specialized environment where microorganisms exist in a sessile, multicellular state, protected by a self-produced matrix of extracellular polymeric substances (EPS) (Flemming & Wingender, 2010). This matrix, consisting of polysaccharides, proteins, and extracellular DNA, acts as a robust physical and chemical barrier against both the host immune system and conventional antimicrobial therapies (Costerton et al., 1999). Biofilms are implicated in a vast majority of human bacterial infections, particularly chronic conditions like cystic fibrosis and infections associated with indwelling medical devices such as catheters and prosthetic joints (NIH, 2021). Therapeutic intervention typically involves the use of matrix-degrading enzymes, such as Dornase alfa, or quorum-sensing inhibitors to prevent or dismantle the biofilm structure (StatPearls, 2023). By disrupting the EPS, these treatments aim to restore the susceptibility of the embedded microbial cells to antibiotics and immune clearance. However, the inherent metabolic heterogeneity and high tolerance of biofilm-resident cells remain significant hurdles in achieving complete eradication (Nature Reviews Microbiology, 2010). This target is considered complex and non-specific as it represents an entire biological community and its environment rather than a single molecular entity.
Degradation of extracellular DNA (eDNA), enzymatic hydrolysis of matrix polysaccharides, inhibition of quorum sensing signaling, and physical or chemical disruption of the extracellular polymeric substance (EPS) to enhance antibiotic penetration and immune access.
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