Enhancing Antimicrobial Peptide Potency through Multivalent Presentation on Coiled-Coil Nanofibrils.

Antibiotic-resistant microbes have become a global health threat. New delivery systems that enhance the efficacy of antibiotics and/or overcome the resistances can help combat them. In this context, we present , a fibril-forming α-helical coiled-coil peptide that functions as an efficient scaffold for the multivalent presentation of the weakly cationic antimicrobial peptide (AMP) . The resulting -decorated coiled-coil fibrils () are nonhemolytic and noncytotoxic and show enhanced antimicrobial activity relative to unconjugated and standard antibiotics against several bacterial strains. Scanning electron microscopy analysis shows that nanofibers disrupt methicillin-resistant membranes, indicating a surface-level mode of action. Furthermore, transmission electron microscopy and circular dichroism studies indicate that decoration of the scaffold with does not alter the secondary-structure propensity or fibril-forming properties of . Thus, the approach reported herein provides a new peptidic scaffold for the multivalent presentation of AMPs to obtain nonhemolytic and noncytotoxic antimicrobial systems with improved efficacy relative to the unconjugated AMP analogues.