Antibacterial and anti-inflammatory properties of host defense peptides against Staphylococcus aureus

Cationic host defense peptides (HDPs) are a promising alternative to antibiotics in the fight against Staphylococcus aureus infections. In this study, we investi-gated the antibacterial and immunomodulatory properties of three HDPs namely IDR-1018, CATH-2, and LL-37. Although all three HDPs significantly inhibited LPS-induced activation of human macrophages, only CATH-2 prevented S. aureus growth. When applied to different infection models focused on intracellularly sur-viving bacteria, only IDR-1018 showed a consistent reduction in macrophage bac-terial uptake. However, this observation did not correlate with an increase in killing the efficiency of intracellular S. aureus. Here, we conclude that despite the promising antibacterial and anti-inflammatory properties of the selected HDPs, macrophages' intrinsic antibacterial functions were not improved. Future studies should either focus on combining different HDPs or using them synergis-tically with other antibacterial agents to improve immune cells' efficacy against S. aureus pathogenesis.