Infections of Drosophila melanogaster with pathogens: Mycobacterium marinum and Burkholderia thailandensis

The first part of this thesis focuses on infection of Drosophila with Mycobacterium marinum. Tuberculosis remains one of the most widespread infectious diseases in the world affecting approximately one third of the world’s population1. The bacterium that causes this serious affliction is Mycobacterium tuberculosis, a Biosafety Level 3 agent. This bacterium’s close relative, M. marinum, causes a tuberculosis-like disease in fish and frogs, but does not require special working conditions. In the fruit fly, Drosophila melanogaster, M. marinum prevents phagosomal acidification, permitting it to survive in fly macrophages. Drosophila is thus a genetically tractable model for the study of some stages of tuberculosis. To understand the pathology of M. marinum infection in the fly, I have analysed the potential role of several genes mainly by survival assays, quantification of antimicrobial peptide expression, and microscopy. A phenotype emerged in a macrophage-specific knockdown of the Drosophila phagocytic receptor Nimrod C3. The second part of this thesis focuses on infections of Drosophila with Burkholderia thailandensis. B. thailandensis is a Gram-negative bacterium closely related to Burkholderia pseudomallei, the causative agent of melioidosis. The study revealed that B. thailandensis was pathogenic in the fly; it activated the fly immune system and antimicrobial peptides were expressed. Despite the strong immune response, this infection is lethal and kills Drosophila within two days. This result suggests that the bacterium is resistant to antimicrobial peptides; similar findings have been reported in the case of the B. pseudomallei resistance to a human antimicrobial peptide in vitro. Overall, this work focuses on host factors involved in immunity to infection and the generation of pathology in intracellular bacterial infections.<br/>In each case, we have used pathogens closely related to serious human pathogens, with the aim of identifying conserved mechanisms of pathogenesis and immunity. Along the way, I have generated several experimental tools that will be useful both for the study of these specific infections and for the analysis of infection biology more generally.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2012

Author dc:creator

• Pilatova, Martina

Advisors dc:contributor.advisor

• Dionne, Marc Stuart
• Bateman, Joseph Matthew

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/e7aa5890-68d4-470d-8c16-58dbc6a7036a

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/e7aa5890-68d4-470d-8c16-58dbc6a7036a