Q fever is a worldwide zoonotic infectious disease caused by the bacterium Coxiella burnetii. During 2007-2010, the largest Dutch Q fever outbreak was reported, reporting more than 4000 human cases. During this outbreak, goats harboring predominantly the CbNL01 genotype strain were identified as the major source of disease in humans and drastic measures such as mass culling of infected goats were implemented to reduce pathogen spread and control Q fever. In order to minimize such complications in the future, it was considered crucial to have a thorough understanding of C. burnetii virulence and to develop effective Q fever vaccines. The causes of the Dutch outbreak were not well-understood and one of the main reasons speculated involved potential hyper-virulence of C. burnetii outbreak strains. This thesis research focused on the characterization of C. burnetii outbreak strains isolated from infected goats, cattle, sheep and clinical human samples. Our studies aimed to better understand bacterial pathogenesis, virulence, evolution and host immune responses, and to identify candidate virulence factors that may have modulated disease outbreak and might have contributed to the increased zoonotic potential of specific strains. The results from this thesis research suggested that virulence potential of C. burnetii strains was mediated by genetic differences between strains associated with mobility of genetic elements and/or differential regulation of gene expression. This thesis research provided a framework for future studies into the development of vaccines and diagnostic tools for Q fever.
Thesis Runa Kuley (click for link thesis)