Abstract 1604 Investigating synergy between DesHDAP2, a novel histone-derived peptide, and different antibiotics

In response to the drug-resistance crisis caused by the overuse of antibiotics, antimicrobial peptides (AMPs) have become a viable alternative treatment. Moreover, when combining AMPs with conventional antibiotics in a cocktail therapy, the two types of therapeutics can be synergetic. However, relatively few systematic studies have been done evaluating which peptide-antibiotic pairings have the greatest synergy. Previous work in the Elmore Lab designed a family of novel histone-derived antimicrobial peptides, DesHDAP1-3. Although DesHDAP2 has been shown to be less potent on its own, preliminary work showed that it nonetheless might be a useful component of cocktail therapy approaches. In this study, we tested the synergy between DesHDAP2 and an array of antibiotics with different mechanisms of action (tetracycline, kanamycin, levofloxacin, rimpacilin, cephalexin, and polymicin B) against E.coli and B.subtilis. DesHDAP2 proved to be synergistic only with tetracycline and additive with kanamycin and rifampicin, while other conventional antibiotics presented an indifferent effect. These results are interesting since the most synergistic combinations arose between antibiotics with an internal bacterial target while the DesHDAP2 peptide permeabilizes the cell membrane. Mixtures of DesHDAP2 with tetracycline and kanamycin at double their MIC do not show cytotoxic activity against human embryonic kidney cells, which further supports the promise of these peptide-antibiotic cocktails as potential therapeutic approaches. This work was supported by NIH/NIAID grant R15 AI169210-01