In the hunt for new antibiotics, people have looked in myriad locations. At the University of Pennsylvania, Cesar de la Fuente’s team goes hunting in the protein world. The researchers aim to find small proteins around 8–50 amino acids long with antimicrobial properties because peptide-based antimicrobials are thought to be less likely to induce resistance than small molecules. In the team’s latest published research, the researchers reprogrammed proteins in wasp venom to create antimicrobial peptides (AMPs) that fight bacteria without also hurting host cells, at least in mice (Cell Rep. Phys. Sci. 2023, DOI: 10.1016/j.xcrp.2023.101459).
The starting point was the venom of the solitary eumenine wasp Eumenes micado. When provoked, their little stingers can deliver a painful cocktail of proteins, but de la Fuente’s team wasn’t looking for pain-producing compounds. Andreia Boaro and Lucía Ageitos, who led the work, took two short venom toxins and, by making different amino acid substitutions, upped the antimicrobial activity and screened out the cytotoxic properties. The synthetic peptides were tested against Gram-negative bacteria in test tubes and in an infected mouse model. While these AMPs won’t become drugs, they could be used as scaffolds for further study, the researchers write in their paper.