Investigation of genes that may contribute to disease tropism in Leishmania species

Saad, Walide I.F (2007) Investigation of genes that may contribute to disease tropism in Leishmania species. MSc(R) thesis, University of Glasgow.

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Abstract

Leishmania parasites cause a wide spectrum of diseases known collectively as the leishmaniases. The three main forms of the disease are cutaneous (CL), mucocutaneous (MCL) and visceral (VL) leishmaniasis and particular species are usually associated with particular disease tropism. A better understanding of the mechanisms of disease would be beneficial in identifying potential drug targets and vaccine candidates. Genome projects for three species have now been completed: L. major (CL), L. infantum (VL) and L. braziliensis (MCL) and analysis of the highly syntenic genomes has revealed a small subset of species specific genes that are hypothesised to contribute in some way to the tropism of that species. Four L. infantum-specific genes were investigated in this project (LinJ28.0330, LinJ36.2750, LinJ20.1200 and LinJ36.2050). All four genes, which are pseudogenes (or absent) in L. major and L. braziliensis, were found to be intact in L. donovani, another species that can cause VL. All genes except LinJ20.1200 are expressed in all three main life cycle stages, procyclic promastigote, metacyclic promastigote and amastigote. LinJ20.1200 appears to be promastigote-specific. LinJ36.2050 encodes a protein that is a putative orthologue of yeast SEC14. A LinJ36.2050 null mutant (DeltaSEC14) was generated. No defect in growth or in vitro infectivity of macrophages phenotype was observed with the ΔSEC14 cells. They were unable to establish cutaneous infection in mice and at the time of writing, it is not yet known if ΔSEC14 clones can be recovered from the spleens of hamsters at 4 months post-infection. Further detailed analysis is required to determine if the ΔSEC14 cells have a phenotype at the cellular level.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: Jeremy Mottram
Keywords: Genetics, Parasitology
Date of Award: 2007
Depositing User: Enlighten Team
Unique ID: glathesis:2007-71164
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 10:49
Last Modified: 10 May 2019 10:49
URI: http://theses.gla.ac.uk/id/eprint/71164

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