Mehta, Meera;
(2021)
Non-Lytic Egress of Mycobacterium Tuberculosis from Human Macrophages.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Macrophages are the target cell for Mycobacterium tuberculosis (Mtb) infection; a major reservoir for productive infection, as well as crucial effector cells for the control of Mtb. However, the majority of bacteria in the caseous necrotic centre of the TB granuloma are extracellular. Extracellular bacteria may arise from host cell necrosis and release of infecting bacteria, but mycobacteria have also been shown to exit from amoeba using a non-lytic strategy and other pathogens have also developed versatile strategies to exit from their host cell, providing an alternative mechanism to escape intracellular restriction. In this thesis I have developed a high throughput flow cytometric assay to quantify intracellular and extracellular bacteria in an in vitro model of human monocyte derived macrophages infected with fluorescent Mtb. I show that extracellular Mtb accumulate in parallel to intracellular bacteria, and make a significant contribution to the overall bacillary burden. These extracellular bacteria do not arise as a result of cellular necrosis in this low multiplicity of infection model. I use computational modelling to predict that a non-lytic process is necessary to explain the observed data. I demonstrate experimentally, for the first time that extracellular Mtb arise by non-lytic egress from human macrophages. I show that this process is related to virulence, since the attenuated Mycobacterium Bovis Bacillus Calmette-Guérin does not display this behaviour.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Non-Lytic Egress of Mycobacterium Tuberculosis from Human Macrophages |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10133980 |
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