On the missing links between the epidemiology and pathophysiology of Staphylococcus aureus

Solomon Abera Mekonnen

    Research output: ThesisThesis fully internal (DIV)

    575 Downloads (Pure)

    Abstract

    The bacterium Staphylococcus aureus is a notorious pathogen that causes dangerous and difficult-to-treat infections. This applies especially to methicillin-resistant S. aureus, better known as MRSA. MRSA infections were originally associated with healthcare settings as a consequence of clinical antibiotic therapy. However, in recent years MRSA infections have become more common among healthy individuals in the community. The community-associated (CA-)MRSA lineages are generally more aggressive than hospital-associated (HA-) lineages. Therefore, it is alarming that such CA-MRSA lineages are now emerging in hospitals. This raises the fundamental question of how CA-MRSA adapts to this new niche. Further, since the originally distinguishing features of CA- and HA-MRSA are losing discriminative value, it is important from a healthcare perspective to identify novel distinctive markers for early recognition and elimination of hospital-adapted CA-MRSA. In the present PhD research, these challenges were tackled with a ‘multi-omics’ approach focused on the USA300 lineage of MRSA, originally identified as CA, but now also causing hospital outbreaks. The results show that hospital-adapted USA300 isolates produce an altered spectrum of virulence factors, changed their metabolism, and exploit human immune cells as a protective environment against antibiotics. Importantly, hospital-adapted CA-MRSA strains can be recognized through distinctive patterns of gene expression and secreted virulence factors. Altogether, these observations show that the epidemic behaviour of MRSA is a multi-factorial trait, and they provide new insights into the missing links between epidemiology and pathophysiology of S. aureus. Moreover, they highlight the benefits of multi-omics technologies for protecting patients and frail individuals against the aggressive CA-MRSA.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • van Dijl, Jan Maarten, Supervisor
    • Volker, Uwe, Supervisor, External person
    • Götz, Friedrich, Assessment committee, External person
    • van Strijp, Jos A. G., Assessment committee, External person
    • Kok, J., Assessment committee
    • Rossen, John, Assessment committee
    Award date8-Oct-2018
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-1104-0
    Electronic ISBNs978-94-034-1103-3
    Publication statusPublished - 2018

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