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

• Published in: iScience 2022-10, Vol.25 (10), p.105211-105211, Article 105211
• Main Authors: Cecotto, Leonardo, van Kessel, Kok, Wolfert, Margreet A., Vogely, Charles, van der Wal, Bart, Weinans, Harrie, van Strijp, Jos, Amin Yavari, Saber
• Format: Article
• Language: English
• Subjects: Immunology; Microbiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105211

Cationic host defense peptides (HDPs) are a promising alternative to antibiotics in the fight against Staphylococcus aureus infections. In this study, we investigated 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 surviving bacteria, only IDR-1018 showed a consistent reduction in macrophage bacterial 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 synergistically with other antibacterial agents to improve immune cells’ efficacy against S. aureus pathogenesis. [Display omitted] •HDPs namely IDR-1018, CATH-2, and LL-37 inhibit macrophage LPS-mediated activation•Only CATH-2 shows direct antibacterial properties against S. aureus•Reduction in the number of phagocytosed bacteria is rendered by IDR-1018•HDPs fail to stimulate macrophage’s ability to kill intracellular S. aureus Immunology; Microbiology