The pathogen Staphylococcus aureus in general, and methicillin-resistant S. aureus (MRSA) in particular, represent serious threats for human health worldwide, causing substantial morbidity and mortality. Over the past decades, the epidemiology of S. aureus has changed drastically especially due to the emergence of highly transmissible community- and livestock- associated lineages, which seriously complicate the fight against this pathogen. It is therefore necessary to develop novel approaches to identify its key determinants for epidemic behavior and virulence, which may serve as markers that distinguish high-risk clones, or as targets for novel anti-staphylococcal interventions. Accordingly, the aim for the present PhD research was to pinpoint the most important virulence factors of two highly transmissible S. aureus lineages that spread among healthy individuals in the community and livestock. To achieve this objective, an effective analysis workflow was established, involving a combination of DNA-based typing approaches, high-throughput proteomics analyses, and two facile infection models. This led to the identification of several critical virulence determinants. An additional aim was to explore bacterial niche adaptations and interactions among pathogenic and commensal bacteria to obtain a better understanding of the fitness of S. aureus in the human host. This was achieved through a detailed analysis of possible changes in S. aureus gene expression, gene regulation, protein composition and virulence upon co-culturing with clinical isolates of Klebsiella oxytoca and Bacillus thuringiensis under infection-mimicking conditions. Altogether, the results presented in this PhD thesis highlight the importance of identifying proteomic signatures to understand and fight highly virulent S. aureus lineages.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2020|