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Title: Case-control study of invasive Staphylococcus aureus disease-host genetic susceptibility and bacterial population structure
Author: Moore, Catrin Elisabeth
ISNI:       0000 0001 3415 8138
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2002
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Staphylococcus aureus is a major pathogen associated with serious community-acquired and nosocomial disease. It is carried nasally at some time by 70% of the population, yet severe disease is relatively uncommon. Two case-control studies were conducted in Oxford, UK and Thailand to examine bacterial and host genetic determinants of severe S. aureus disease. Over 800 cases and 1,600 healthy control individuals were recruited into the two studies. The genetic population structures of S. aureus disease and carriage isolate populations from the Oxford study were studied and compared using phage typing, pulsed-field gel electrophoresis, and multilocus sequence typing. Natural populations of S. aureus have a well-defined clonal population structure, but there was no evidence for the existence of hypervirulent clones. The presence or absence of 33 putative bacterial virulence determinants was examined. After adjusting for the effect of clonality, seven determinants (fhbA, cna, sdrE, sej, eta, hlg and ica) were significantly more common in invasive isolates; all contributed independently to virulence. In the host genetic studies a functional single nucleotide polymorphism at amino acid position 131 of the Fc gamma receptor IIA (FcyRIIA) gene was significantly associated with severe disease. In addition an additive x additive epistatic interaction was found between this FcyRIIA polymorphism and the functional FcyRIIIB NA1/NA2 polymorphism. These significant associations were present when community-acquired disease cases were considered alone, but absent in hospital-acquired disease cases. The putatively functional polymorphisms in genes coding for mannose binding lectin and Tolllike receptor 2 were not associated with disease. Both bacterial and host factors are important in determining the occurrence of severe S. aureus disease. In hospital-acquired infection it is likely that acquired host, bacterial and environmental factors predominate, lessening the importance of any host genetic component.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Bacteria