Identification and characterization of broad-spectrum cathelicidin family antimicrobial peptides from the pygmy sperm whale Kogia breviceps.

Cathelicidins are crucial antimicrobial peptides (AMPs) that play a key role in the innate immunity of marine vertebrates. The pygmy sperm whale (Kogia breviceps), which resides in environments populated by diverse microbial communities, faces complex pathogenic threats; however, its cathelicidin family AMPs remain uncharacterized. In this study, we identified three novel cathelicidin peptides-Kb4-1, Kb4-2, and Kb5 from the whale (Kogia breviceps). All three peptides exhibited broad-spectrum and potent antibacterial activity, with Kb5, an amphipathic α-helical peptide, showing the strongest and fastest bactericidal effect. Moreover, these peptides effectively inhibited biofilm formation, disrupted pre-established biofilms, and eradicated bacterial persister cells. Notably, Kb5 induced the most pronounced bacterial membrane disruption among the three peptides. Additionally, all peptides exerted their antibacterial effects, at least partially, through the interaction with bacterial DNA and the consequent induction of reactive oxygen species (ROS) production. In a S. aureus-induced murine peritonitis model, Kb5 treatment significantly reduced bacterial load and improved survival rates in mice. These findings highlight the therapeutic potential of Kb5 and enhance our understanding of host defense mechanisms in marine mammals living in challenging environments.