|Title:||Mycobacterium tuberculosis-Host Interactions: Bacterical Requirements for chronic infection and host plasmin (ogen) induced dissemination|
|Publisher:||University of Sydney.|
Faculty of Medicine.
Mycobacterial Research Laboratory.
|Abstract:||Infection with M. tuberculosis commonly results in latent infection where bacteria remain non-infectious in a non-replicative estate, from which reactivation to active disease can occur. The work presented here, identified a set of 260 genes that were essential for the bacteria to survive during latency and cause reactivation in a murine latency model. Although TB is primarily a pulmonary infection, the bacteria can disseminate to seed virtually any organ and tissue. The mechanisms by which M. tuberculosis spreads from the original site of infection remain unclear. Plasminogen (plg) is the main component of the human fibrinolytic system. We have demonstrated, with both confocal microscopy and direct enzymatic assay, that M. tuberculosis binds human plg preferentially to that of the mouse. A transgenic humanised plg+/+ mouse was created and infected; results indicate enhanced dissemination to the liver following a low dose aerosol infection. Furthermore, clinical isolates from cases of human extra pulmonary TB, have shown an increased ability to bind plg to the bacterial surface. Improved knowledge of these important pathogenic processes, establishment of latency and reactivation through disseminated bacteria, is not only essential to our understanding of TB, but may also lead to novel preventative and treatment strategies.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|MONTELEONE Maria - Final thesis.pdf||Final thesis||179.46 MB||Adobe PDF|
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