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Staphylococcus aureus biofilm is a complex, multicellular community of bacteria encased in a self-produced extracellular polymeric substance (EPS) matrix composed of polysaccharides (PIA/PNAG), proteins (Bap, FnBPs), and extracellular DNA (eDNA) [15, 17, 19]. This structure serves as a critical virulence factor, providing a protective barrier that renders the bacteria up to 1,000 times more resistant to conventional antibiotics and host immune responses compared to their planktonic counterparts [3, 9, 20]. Biofilms are a primary cause of chronic and recalcitrant infections, particularly those associated with indwelling medical devices such as catheters, heart valves, and prosthetic joints, as well as deep-seated conditions like osteomyelitis and endocarditis [2, 12, 16]. Therapeutic interventions aim to prevent initial bacterial attachment, degrade the protective matrix, or inhibit quorum sensing pathways that regulate biofilm maturation and dispersal [4, 6, 8]. Key agents include matrix-disrupting enzymes like Dispersin B and specialized antibiotics such as Daptomycin and Rifampicin, which are often used in combination to penetrate the dense matrix and target dormant persister cells [5, 10, 20]. However, the risk of systemic bacterial dissemination during biofilm disruption and the rapid emergence of resistance remain significant hurdles in clinical management [1, 12, 20].
Inhibition of initial bacterial adhesion to surfaces, enzymatic degradation of the extracellular polymeric substance (EPS) matrix, inhibition of quorum sensing (QS) signaling pathways (e.g., agr or traP systems), disruption of iron metabolism, and targeting of dormant persister cells within the biofilm structure [4, 6, 7, 10].
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