Antibacterial and anti-inflammatory properties of host defense peptides against Staphylococcus aureus
Leonardo Cecotto,
Kok van Kessel,
Margreet A. Wolfert,
Charles Vogely,
Bart van der Wal,
Harrie Weinans,
Jos van Strijp,
Saber Amin Yavari
Affiliations
Leonardo Cecotto
Department of Orthopedics, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands; Department of Medical Microbiology, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands; Corresponding author
Kok van Kessel
Department of Medical Microbiology, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Margreet A. Wolfert
Department of Chemical Biology and Drug Discovery, Utrecht University, 3508GA Utrecht, the Netherlands
Charles Vogely
Department of Orthopedics, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Bart van der Wal
Department of Orthopedics, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Harrie Weinans
Department of Orthopedics, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands; Department of Biomechanical Engineering, Delft University of Technology, 2628CD Delft, the Netherlands
Jos van Strijp
Department of Medical Microbiology, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Saber Amin Yavari
Department of Orthopedics, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands; Regenerative Medicine Centre Utrecht, Utrecht University, 3508GA Utrecht, the Netherlands; Corresponding author
Summary: 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.
