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Project

Characterization of the parasite-related factors associated with the visceralization capacity of Leishmania donovani.

Leishmania donovani is a protozoan parasite that is usually the causative agent of visceral leishmaniasis (VL), aninfectious disease which is fatal if left untreated and affects internal organs such as liver, spleen and bone marrow. In some cases, however, infection with this specific parasite species is relatively benign and only causes cutaneous lesions which are comparable with the lesions from parasite species causing cutaneous leishmaniasis (CL). Although some parasite-specific genes have been implicated in the visceralizing capacity of L. donovani, the associated phenotypic factors that are responsible for this change in tissue tropism are not well-understood. Past research already compared some phenotypic features, such as resistance to increasing temperatures and oxidative stress, between VL-causing L. donovani parasites and CL–causing L. major parasites. However, because of their evolutionary distance comparing different parasite species may not be completely correct as next to genetic variations, also phenotypic discrepancies unrelated to human pathology could be present.Therefore, this study aims at identifying the parasite-related phenotypic factors associated with visceralization byusing two isogenetic strains. These will be created by phenotype-driven passive parasite selection from the targetorgans involved (skin vs. spleen) in the in vivo hamster model. After repeated selection of parasites with a specifictissue tropism and subsequent population enrichment, the course of infection with both the VL-causing and CLcausing parasites will be evaluated and compared by bioluminescence imaging. To characterize both parasitepopulations, the expression levels of A2, a virulence factor that has been associated with visceralization, will becompared and the strains will be characterized phenotypically in order to identify possible pitfalls during thevisceralization process.
Date:1 Apr 2018 →  31 Mar 2019
Keywords:BIOLUMINESCENCE IMAGING, VECTOR-BORNE INFECTIONS, SELECTION PROCEDURES, PHENOTYPIC VARIATION
Disciplines:Microbiology, Veterinary medicine