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Clostridioides difficile surface proteins, primarily the Surface Layer Protein A (SlpA), constitute a paracrystalline array that covers the entire bacterial cell. These proteins play a fundamental role in the pathogenesis of C. difficile infection (CDI) by mediating the initial stages of colonization, specifically the adhesion of the bacterium to the host's colonic epithelium (Kirk et al., 2017, PubMed: 28630186). Beyond structural integrity, certain surface proteins like Cwp84 function as proteases that process other cell wall components, while others like Cwp66 act as adhesins (Péchiné et al., 2018, PubMed: 29332434). Because these proteins are highly exposed on the bacterial surface, they are prime targets for the development of vaccines and monoclonal antibodies aimed at preventing colonization and promoting bacterial clearance. Therapeutic strategies targeting these proteins often focus on neutralizing their adhesive properties or inducing a robust humoral immune response to facilitate opsonophagocytosis, thereby reducing the severity and recurrence of CDI (Valneva, 2015, ClinicalTrials.gov: NCT02316470). The diversity of these proteins across different strains remains a challenge for broad-spectrum vaccine efficacy, but they remain a critical focus for non-toxin-based therapeutic interventions (Crobach et al., 2016, PubMed: 27553431).
Inhibition of bacterial adhesion to host intestinal epithelium and induction of opsonophagocytic immune responses.
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