Abstract
Leishmania parasites cause outstanding levels of morbidity and mortality in many developing countries in tropical and subtropical regions. Numerous gene expression profiling studies have been performed comparing different Leishmania species’ life-cycles and stage forms in regard to their distinct infective ability. Based on expression patterns, homology to human orthologues, in silico HLA-binding predictions, and annotated functions, we were able to select several vaccine candidates which are currently under study. One of these candidates is the Leishmania infantum ubiquitin-conjugating enzyme E2 (LiUBC1), whose relative levels, subcellular location, in vitro infectivity in the U937 myeloid human cell model, and protection levels in Syrian hamsters against L. infantum infection were studied herein. LiUBC1 displays a low level of similarity with the mammalian orthologs and relevant structure differences, such as the C-terminal domain, which is absent in the human ortholog. LiUBC1 is present in highly infective promastigotes. Knock-in parasites overexpressing the enzyme increased their infectivity, according to in vitro experiments. Syrian hamsters immunized with the recombinant LiUBC1 protein did not show any parasite burden in the spleen, unlike the infection control group. The IFN-γ transcript levels in splenocytes were significantly higher in the LiUBC1 immunized group. Therefore, LiUBC1 induced partial protection against L. infantum in the Syrian hamster model.
Highlights
Leishmaniasis is a disease caused by trypanosomatid parasites from the genus Leishmania
visceral leishmaniasis (VL) caused by Leishmania infantum is a zoonosis (ZVL), whereas VL caused by L. donovani is anthroponotic
The protein structure of LiUBC1, predicted based on the data obtained from S. cerevisiae and H. sapiens orthologs, showed a C-terminal end very similar to that observed in the yeast protein, which is not present in the human enzyme (Figure 2)
Summary
Leishmaniasis is a disease caused by trypanosomatid parasites from the genus Leishmania. VL caused by Leishmania infantum is a zoonosis (ZVL), whereas VL caused by L. donovani is anthroponotic. The promastigotes are fusiform motile cells with a flagellum emerging from the cellular body anterior pole This stage differentiates into the procyclic form in the sand fly gut, with low infective ability; this form migrates towards the anterior part of the gut, transforming into a highly infective form called metacyclic. These promastigotes are inoculated in the mammalian host’s dermis during blood meal intake. The sand fly be-comes infected by feeding from an infected mammal’s blood, completing the parasite cycle [15]
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