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Publication Abstract from PubMed

Vibrio cholerae, the causative agent of cholera, uses surface proteins such as the repeats-in-toxin (RTX) adhesin FrhA to colonize hosts and initiate infection. Blocking bacterial adhesion represents a promising therapeutic strategy to treat infections without promoting drug resistance. FrhA contains a peptide-binding domain (PBD) that is key for hemagglutination, human epithelial cell binding, and V. cholerae biofilm formation. Previous studies identified a lead pentapeptide ligand with the sequence Ala-Gly-Tyr-Thr-Asp (AGYTD) that blocks V. cholerae colonization of the mouse small intestine at high micromolar concentrations. In this study, a structure-guided approach identified a minimal D-amino acid-containing tripeptide motif with higher affinity for the FrhA-PBD and predicted metabolic stability. Our results contribute to the development of anti-adhesion strategies to combat infections. Impact statement Our study elucidates the molecular basis of peptide recognition by the Vibrio cholerae adhesin FrhA and develops minimal D-amino-acid peptides that block adhesion with nanomolar affinity. These findings advance understanding of RTX adhesins and provide a structural blueprint for next-generation anti-adhesion therapeutics against cholera and related infections.

Peptide-based ligand antagonists block a Vibrio cholerae adhesin.,Wang M, Du G, Yongo-Luwawa C, Lu A, Kinrade B, Munro K, Klose KE, Lubell WD, Davies P, Guo S FEBS Lett. 2025 Nov 20. doi: 10.1002/1873-3468.70231. PMID:41262002^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.