| Итог: | <p><em>Staphylococcus aureus</em> is a worldwide leading cause of skin and soft tissue, bone and joint, and bloodstream infection. Despite this, <em>S. aureus</em> is also a harmless commensal in about one third of the population, although carriage is a risk factor for subsequent disease. <em>S. aureus</em> has evolved resistance to several antibiotics, including meticillin, resulting in meticillin-resistant <em>S. aureus</em> (MRSA), which in the UK largely consists of two epidemic lineages. In spite of much research, substantial aspects of the epidemiology and biology of <em>S. aureus</em> are still poorly understood.</p><p>In investigating the <em>S. aureus</em> host-organism relationship, this thesis has three aims. To explore the interface between community and hospital-acquired <em>S. aureus</em>; to investigate the carriage dynamics of <em>S. aureus</em> in the community; and to use population genetic methods to study epidemic hospital associated <em>S. aureus</em> lineages.</p><p>Case-control studies comparing hospital and community-acquired MRSA revealed that the majority of UK MRSA remains healthcare associated, with community-acquired MRSA reliably identified in only 0.2% of individuals. However, an additional 0.2% of individuals also carried "feral" MRSA with molecular characteristics identical to hospital-associated strains, but in hosts with no healthcare risk factors. To further investigate <em>S. aureus</em> carriage dynamics in the community, a carriage study was designed to collect detailed host factor information and correlate this with <em>S. aureus</em> carriage over time. In the study 32% of participants carried <em>S. aureus</em> of which the majority carried for over one year. Younger age was associated with transient carriage, including S. aureus acquisition in individuals who were initially negative. Finally, whole-genome sequencing of two epidemic <em>S. aureus</em> lineages indicated rapid clonal expansion of MRSA and clear geographic and temporal genetic structure. One particularly closely related cluster of strains may provide a genetic explanation for an MRSA outbreak in Brighton.</p>
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