From In Vitro Promise to In Vivo Reality: An Instructive Account of Infection Model Evaluation of Antimicrobial Peptides

Antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics in the face of ever-increasing resistance. Our research has focused on crotalicidin (Ctn), an AMP from a snake venom, and a fragment thereof, Ctn[15-34], with improved in vitro antimicrobial and anticancer activities and remarkable serum stability. As the retroenantio versions of both AMPs maintained favorable profiles, in this work we evaluate the in vivo efficacy of both the na-tive-sequence AMPs and their retroenantio counterparts in a murine infection model with Aci-netobacter baumannii. A significant reduction in bacterial levels is found in the mice treated with Ctn[15-34]. However, contrary to expectations, the retroenantio analogues either exhibit toxicity or lack efficacy when administered to mice.