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The bacterial biofilm extracellular matrix (ECM), also known as extracellular polymeric substances (EPS), is a complex, self-produced scaffold composed of polysaccharides, proteins, extracellular DNA (eDNA), and lipids (Flemming & Wingender, 2010, Nature Reviews Microbiology). Its primary biological function is to provide structural stability to the bacterial community and act as a protective barrier against host immune defenses and antimicrobial penetration (Flemming et al., 2016, Nature Reviews Microbiology). In clinical settings, the ECM is a major factor in the persistence of chronic infections, such as those in cystic fibrosis, chronic wounds, and medical device-related infections, by conferring up to 1000-fold higher antibiotic tolerance compared to planktonic cells (Hall & Mah, 2017, Physiological Reviews). Therapeutic targeting of the ECM involves enzymatic degradation of its components—for example, using Dornase alfa to cleave eDNA or glycoside hydrolases to break down polysaccharides—thereby priming the biofilm for clearance by antibiotics or the immune system (Karygianni et al., 2020, Frontiers in Microbiology). Additionally, chelating agents like EDTA are used to disrupt the ionic cross-linking of the matrix, further destabilizing the biofilm architecture (Driffield et al., 2008, Antimicrobial Agents and Chemotherapy). This strategy aims to transition bacteria from a protected, sessile state back to a vulnerable, planktonic state. However, the heterogeneity of matrix composition across different species remains a significant challenge for universal therapy.
Enzymatic degradation of extracellular polymeric substances (e.g., eDNA, polysaccharides) or chelation of stabilizing divalent cations to destabilize the biofilm structure and enhance antibiotic penetration (Flemming et al., 2016; Karygianni et al., 2020).
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