DesHDAP2 Shows Significant Synergy with Conventional Antibiotics, Despite Its Relatively Low Potency.

Antimicrobial peptides (AMPs) represent a potential tool in combating increasing antibiotic resistance in bacteria. One promising application of AMPs is their use in antibacterial cocktails along with conventional, small-molecule antibiotics. Here, we investigate the potential antibacterial synergy of our novel histone-derived AMP, DesHDAP2. Consistent with previous studies, DesHDAP2 has relatively low antimicrobial activity on its own, particularly against Gram-negative bacteria. However, DesHDAP2 demonstrates antibacterial synergy with four antibiotics representing several different mechanisms of action, kanamycin, tetracycline, levofloxacin, and polymyxin B. Combinations of DesHDAP2 with these antibiotics also did not show any appreciable cytotoxicity against eukaryotic cells. These results highlight the promise of DesHDAP2 in combination therapy. Moreover, they emphasize the potential application of AMPs that have relatively low activity on their own in therapeutic cocktails with other antibiotics.