Conformations and sequence determinants in the lipid binding of an adhesive peptide derived from Vibrio cholerae biofilms.

Surface adhesion is critical to the survival of pathogenic bacteria both in natural niches and during infections, often via forming matrix-embedded communities called biofilms. Vibrio cholerae, the causal agent of pandemic cholera, is capable of forming biofilms adhering to both biotic and abiotic surfaces and the biofilm lifestyle has been implicated in promoting the survival of V. cholerae both in the natural reservoir and during host colonization. Previously, a 57-amino acid loop in the biofilm-specific adhesin Bap1 (Bap1-57aa) has been identified as a key contributor to the adhesion of V. cholerae biofilms to various surfaces including lipid membranes. However, the mechanism underlying its interaction with lipids, as well as its secondary structures, remain unresolved. Here, we combined biophysical, computational, and genetic approaches to elucidate the molecular mechanism of how this adhesive peptide interacts with lipids and lipid-coated surfaces. We found that a central aromatic-rich motif anchors the peptide to lipid bilayers while peripheral pseudo repeats enhance binding through avidity. Surprisingly, the core motif undergoes a lipid-induced conformational transition into a β-hairpin, enabling robust membrane insertion. We confirmed these findings both in vitro and in the biofilm context. Moreover, we demonstrated that the adhesive peptide can adhere to model host surfaces and is sensitive to membrane curvature. Finally, we show that the biofilm-derived peptide is found in several other Vibrio species, and its sequence is well-conserved. Our results provide molecular insight into biofilm adhesion and may lead to new strategies for targeted biofilm removal, as well as the design of bioinspired underwater adhesives.