Engineering of antimicrobial peptide fibrils with feedback degradation of bacterial-secreted enzymes
Fenghua Wang, Wencheng Xia, Mingming Zhang, Rongrong Wu, Xiaolu Song, Yun Hao, Yonghai Feng, Liwei Zhang, Dan Li, Wenyan Kang, Cong Liu, Lei Liu
Abstract
steric zipper-like interactions. The enzyme-cleavage segment was partially involved in self-assembly, but also exhibited high flexibility in the fibril structure, with accessibility to gelatinase binding and degradation. Moreover, we applied the EAP fibril as a tunable scaffold for developing degradable self-assembled antimicrobial fibrils (SANs) by integrating melittin and EAP together. SANs exhibited superior activity for killing bacteria, and significantly improved the stability and biocompatibility of melittin. SANs were eliminated automatically by the gelatinase secreted from targeted bacteria. Our work provides a new strategy for rational design of functional fibrils with a feedback regulatory loop for optimizing the biocompatibility and biosafety of designed fibrils. Our work may aid further developments of "smart" peptide-based biomaterials for biomedical applications.