Staphylococcus aureus is a major bacterial pathogen that represents a significant burden for human health, especially due to its high resistance to antibiotics. Therefore, new alternative approaches to protect patients and frail individuals against multi-drug resistant S. aureus are urgently needed. This could be achieved through passive or active immunization against this bacterium. Proteins that are exposed on the bacterial cell surface, or particular surface-exposed protein domains, are readily accessible to the host immune system and they are, therefore, attractive candidate targets for active or passive immunization. Accordingly, the present PhD research was aimed at identifying the most promising targets for novel anti-staphylococcal immunotherapies. This turned the focus of research towards cell surface-exposed immunodominant proteins of S. aureus, in other words the ‘immuno-surfacome’. In a first approach, the immuno-surfacome was mapped by mass spectrometry, which presented a possible road map towards the development of anti-staphylococcal immunotherapies and highlighted peptidoglycan hydrolases as attractive potential targets due to their cell surface exposure and important biological activities in the staphylococcal life cycle. Subsequent studies identified immunodominant surface-exposed domains of such peptidoglycan hydrolases, as well as their contributions to cell division and antibiotic resistance. This actually implies that these enzymes could also serve as targets for novel antibiotics or for molecules that potentiate existing antibiotics. Due to their cell wall-degrading activities some peptidoglycan hydrolases may even be used as antimicrobials themselves. Altogether, the present PhD research provides important leads for the development of novel approaches to fight infections caused by multi-drug resistant S. aureus.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||16-feb.-2022|
|Plaats van publicatie||[Groningen]|
|Status||Published - 2022|