Saving Private Macrophage: Alternative therapeutic options for Staphylococcus aureus implant-associated infections

Leonardo Cecotto

    Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

    3 Downloads (Pure)

    Abstract

    Breaking a bone is not a pleasant experience. It might get worse if an implant is needed to repair the fracture. In 1 to 5% of the cases, Staphylococcus aureus might use the implant to enter and colonize our organism. This pathogenic bacterium is extremely difficult to kill due to its resistance to common antibiotic treatments. We need to find new therapeutic strategies to prevent S. aureus from entering and surviving inside our bodies.
    Nature provided means to combat pathogenic bacteria even before antibiotic discovery: our immune system is an example. In the context of implant-associated infections, macrophages are a key immune cell type that coordinates the healing process while defending our organism from external threats. As this is already a lot of work, they need extra help to protect us from threats as dangerous as S. aureus. In this work, we aim to support macrophages in their fight against pathogens by increasing their antibacterial functions.
    We tried to stimulate macrophages with several compounds known for their antibacterial properties, such as silver ions and nanoparticles, host defense peptides, and S. aureus-specific antibodies. Unfortunately, none of these strategies alone succeeded in helping macrophages eliminate all bacteria. However, a combination of those, might hold the key to successful therapy.
    In conclusion, we focused on one cell type. However, implant-associated infections represent a complex scenario, with multiple players involved and all in need of help. Saving macrophages might help us win the fight, but not the war against S. aureus infections.v
    Original languageEnglish
    Awarding Institution
    • University Medical Center (UMC) Utrecht
    Supervisors/Advisors
    • van Strijp, Jos, Primary supervisor
    • Weinans, Harrie, Supervisor
    • Amin Yavari, Saber, Co-supervisor
    • van der Wal, Bart, Co-supervisor
    Award date11 Sept 2023
    Publisher
    Print ISBNs978-90-393-7576-1
    DOIs
    Publication statusPublished - 11 Sept 2023

    Keywords

    • innate immune system
    • macrophages
    • neutrophils
    • Staphylococcus aureus
    • mesenchymal stem cells
    • implant-associated infections
    • silver
    • host defense peptides
    • monoclonal antibodies
    • multicellular in vitro model

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