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Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium recognized as a keystone pathogen in the pathogenesis of chronic periodontitis (Hajishengallis et al., 2012). The cell membrane and its associated subgingival biofilm constitute a complex therapeutic target, as they provide structural integrity and a protective environment that shields the bacteria from host immune responses and antimicrobial treatments (Marsh & Zaura, 2017). The cell membrane is characterized by the presence of potent virulence factors, including lipopolysaccharides (LPS), fimbriae, and gingipains, which are essential for tissue degradation and nutrient acquisition (How et al., 2016). Targeting this assembly involves the use of mechanical debridement, local or systemic antibiotics, and novel small-molecule inhibitors like atuzaginstat that disrupt specific virulence mechanisms (Dominy et al., 2019). Furthermore, the persistence of P. gingivalis in subgingival biofilms has been linked to systemic inflammatory conditions, including cardiovascular disease and Alzheimer's disease, making its eradication a priority in periodontal therapy (Slots, 2017). Effective management requires overcoming the physical barrier of the biofilm matrix to deliver therapeutic concentrations of drugs to the underlying bacterial cells.
Drugs targeting this complex act through various mechanisms including the disruption of cell membrane integrity, inhibition of bacterial protein or DNA synthesis, and the neutralization of secreted virulence factors like gingipains (How et al., 2016). Anti-biofilm agents specifically aim to degrade the extracellular polymeric substance (EPS) matrix to enhance antibiotic penetration and facilitate bacterial clearance (Marsh & Zaura, 2017).
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