Two distinct amphipathic peptide antibiotics with systemic efficacy
Jayaram Lakshmaiah Narayana, Biswajit Mishra, Tamara Lushnikova, Qianhui Wu, Yashpal S. Chhonker, Yingxia Zhang, D. Zarena, Evgeniy S. Salnikov, Xiangli Dang, Fangyu Wang, Caitlin N. Murphy, Kirk Foster, Santhi Gorantla, Burkhard Bechinger, Daryl J. Murry, Guangshun Wang
Abstract
Significance It is the dream of many scientists to develop antimicrobial peptides (AMPs) into potent antibiotics to combat resistant pathogens and their biofilms. However, the success is low due to limited knowledge on peptide design. Natural AMPs are diverse in sequence, activity, and source. We found a linear relationship between the averaged contents of arginine (R) and hydrophobic amino acids (Pho) of over 3,000 AMPs in the current Antimicrobial Peptide Database ( http://aps.unmc.edu/AP ). Based on this R–Pho relationship, we identified a peptide template and designed two representative amphipathic peptides with distinct structures and activities. Remarkably, horine and verine showed systemic efficacy in mice, but no nephrotoxicity to rodents. Our study advances peptide design and provides two antibiotics to combat drug-resistant pathogens.