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Extracellular polymeric substances (EPS) constitute the self-produced, complex matrix that encases bacterial cells within a biofilm, often representing up to 90% of the total organic matter [1.1.3, 1.2.2]. This matrix is primarily composed of polysaccharides, proteins, extracellular DNA (eDNA), and lipids, which together provide structural stability and facilitate adhesion to surfaces [1.2.3, 1.4.1]. EPS serves as a formidable physical and chemical barrier, protecting the embedded bacteria from host immune cells and significantly reducing the penetration of antimicrobial agents [1.2.4, 1.4.3]. This protective role is a major factor in the development of chronic, recalcitrant infections, such as those found in cystic fibrosis, chronic wounds, and on indwelling medical devices [1.2.1, 1.3.2]. Therapeutic interventions targeting EPS focus on degrading its components—using enzymes like dornase alfa for eDNA or glycoside hydrolases for polysaccharides—or inhibiting its synthesis to disrupt biofilm integrity [1.3.2, 1.3.5]. By weakening the EPS matrix, these strategies aim to restore the efficacy of conventional antibiotics and enhance the host's ability to clear the infection [1.3.2, 1.3.3].
Drugs targeting EPS act through the enzymatic degradation of matrix components such as eDNA, polysaccharides, and proteins, or by inhibiting the synthesis and assembly of these polymers [1.3.1, 1.3.2, 1.3.3]. Additionally, chelating agents like EDTA disrupt the matrix by removing divalent cations (e.g., Ca2+, Mg2+) that provide structural cross-linking and stability [1.1.2, 1.3.1]. Some antibiotics, such as macrolides, can also inhibit the production of specific EPS components like alginate [1.3.1].
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