Fig. 3

Schematic representation of anti-virulence strategies covered under this review. 1. Targeting virulence factor: (a) Protease Inhibitors: Microbial protease plays an essential role in the progression of periodontal diseases and thus could be a potential therapeutic target. The therapeutic approach focused on Gingipain inhibitor (Kgp specific inhibitor A71561) can significantly decrease virulence. (b) LPS inhibition: Cell surface components like LPS could be targeted for treating periodontal diseases. α-Tocopherol reduces inflammatory cytokines while increasing antimicrobial peptides, and β-defensins, thereby counteracting the damaging effects of LPS, which play a vital role in the pathogenesis of periodontal diseases. (c) Inhibition of fimbrial assembly: Fimbriae are a major structural component of periodontal bacteria. Studies have shown that peptides originating from the conserved C-terminal of FimA and Mfa1 subunits prevent the fimbrial assembly of P. gingivalis and interfere with biofilm formation. (d) Targeting IL-1β as a potential therapy: It has been shown that the capsular polysaccharide upregulates the expression of IL 1-β by activating the JNK pathway in macrophages. Increased IL 1- β levels lead to inflammation and bone resorption, indicating a possible therapeutic strategy to combat this periodontal pathogen. (e) Toxin inhibition by receptor-based peptide: A. actinomycetemcomitans, associated with periodontal disease, produces leukotoxin (LtxA) during colonization in the host to escape the host immune response. LtxA is the critical virulence factor of A. actinomycetemcomitans, which kills leukocytes by recognizing cholesterol and the β2 strands of lymphocyte function-associated antigen-1 (LFA-1) integrin. Molecular inhibitors mimic the target to compete for toxin binding, thus neutralizing toxin binding activity. Small synthetic receptor-specific peptides can hinder LtxA-mediated cytotoxicity by binding to the β domain of transmembrane protein LFA-1. 2. Targeting quorum sensing signalling: QS is the most distributed and studied bacterial communication, which helps periodontal bacteria communicate with each other through signalling molecules and behaviour coordination. Various compounds can block quorum-sensing signals produced by periodontal pathogens, thus inhibiting the disease progression pathway