Leishmania infantum is the etiologic agent of zoonotic visceral leishmaniasis in the mediterranean basin and is transmitted by the bite of phlebotominae sandflies during bloodmeal intakes. The life cycle of the parasite is dimorphic and digenetic because the extracellular promastigote alternates with the intracellular amastigote stage in the gut of the vector insect and inside mammalian phagocytes respectively. The aim of this PhD Thesis is the comparative transcriptome analysis of the basic differentiation stages of the parasite and several envirnomental factors affecting growth and differentiaton. For this purpose, whole-genome shotgun DNA microarrays were constructed from a complete genome library and gene expression profile analysis were performed by combined hybridization of cDNA samples to be compared and the subsequent normalization and statistical analysis. In addition to the wide number of data obtained, general information about the differentiation of the parasite could be extracted: the down-regulation rate is higher in the amastigote than in the promastigote stage, L. infantum PNA promastigotes are more infective than PNA promastigotes, provided the differential expression profile of several genes and the results of the in vitro infection assay, temperature increase is more influencing than pH decrease in the differentiation process of promastigotes to amastigotes and a considerable number of differentially regulated genes has been found between promastigotes extracted from the anterior gut of the insect vector and axenically cultured promastigotes in stationary phase.

Beca predoctoral I3P (Itinerario Integrado de Inserción Profesional) del CSIC

292 p.-74 fig.-39 tab.-11 anexos.

Peer reviewed