Leishmania is a dimorphic parasitic protozoan which exists as a flagellated promastigote in the sandfly vector and as an intracellular amastigote in the phagolysosomal compartment of mammalian host macrophages. It is the amastigote form that is responsible for the pathology in susceptible vertebrate hosts. Leishmania donovani is responsible for visceral leishmaniasis, the most severe form of the leishmanial diseases. We have investigated the antibody response against an amastigote-specific protein, A2, which is developmentally expressed in L. donovani during promastigote-to-amastigote cytodifferentiation. A2 is conserved in L. donovani and L. mexicana species but not in other Leishmania species tested. We have shown that this characteristic contributes to its potential as a useful specific diagnostic antigen for visceral leishmaniasis. Developmental expression of A2 involves A2 mRNA untranslated regions (UTRs) and we have demonstrated that A2 UTRs can regulate expression of exogenous suicide genes throughout the Leishmania life cycle. We have shown that the A2 gene regulatory system has potential for the generation of developmentally attenuated L. donovani strains. Finally, we have performed a preliminary characterization of a gene, A2rel, that is tandemly associated with A2 genes in the genome. Contrary to A2 genes, the A2rel gene is well conserved in the Leishmania species. Although A2rel does not share sequence similarity with any known leishmanial genes characterized to date, it does appear to share characteristics with membrane-bound glycoproteins.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34966 |
| Date | January 1997 |
| Creators | Ghedin, Elodie. |
| Contributors | Matlashewski, Greg (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Institute of Parasitology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001617095, proquestno: NQ44438, Theses scanned by UMI/ProQuest. |
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