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

doi:10.1016/j.isci.2022.105211

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

iScience. 2022 Sep 24;25(10):105211. doi: 10.1016/j.isci.2022.105211. eCollection 2022 Oct 21.

Authors

Leonardo Cecotto^{1

2}, Kok van Kessel², Margreet A Wolfert³, Charles Vogely¹, Bart van der Wal¹, Harrie Weinans^{1

4}, Jos van Strijp², Saber Amin Yavari^{1

5}

Affiliations

¹ Department of Orthopedics, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands.
² Department of Medical Microbiology, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands.
³ Department of Chemical Biology and Drug Discovery, Utrecht University, 3508GA Utrecht, the Netherlands.
⁴ Department of Biomechanical Engineering, Delft University of Technology, 2628CD Delft, the Netherlands.
⁵ Regenerative Medicine Centre Utrecht, Utrecht University, 3508GA Utrecht, the Netherlands.

Abstract

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.

Keywords: Immunology; Microbiology.