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Leishmaniasis

Leishmaniasis

Leishmaniasis is a protozoal disease caused by species of the genus Leishmania and transmitted through the bite of infected female sandflies. The parasite exists in two principal morphological forms during its life cycle. A sandfly acquires intracellular amastigotes from an infected reservoir host, such as a dog. Within the sandfly, these forms differentiate into motile, flagellated promastigotes. During a subsequent blood meal, promastigotes are injected into the human host, where they...

Antiprotozoal Agents

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...

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Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major

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Leishmania express a functional Cdc20 homologue.

Tamar Listovsky¹, Michael Brandeis, Dan Zilberstein

¹Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.

Biochemical and Biophysical Research Communications

|April 5, 2011

Summary

This summary is machine-generated.

Leishmania donovani parasites utilize a Cdc20 protein to regulate their cell cycle. This protein controls the Anaphase Promoting Complex/Cyclosome (APC/C) for cell cycle progression.

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A Parasite Rescue and Transformation Assay for Antileishmanial Screening Against Intracellular Leishmania donovani Amastigotes in THP1 Human Acute Monocytic Leukemia Cell Line

A Parasite Rescue and Transformation Assay for Antileishmanial Screening Against Intracellular Leishmania donovani Amastigotes in THP1 Human Acute Monocytic Leukemia Cell Line

Published on: December 30, 2012

Area of Science:

Cell Biology
Parasitology
Molecular Biology

Background:

Cell cycle regulation mechanisms in Trypanosometidae, including Leishmania donovani, are poorly understood.
Leishmania donovani causes visceral leishmaniasis (kala azar), a severe human disease.

Purpose of the Study:

To investigate the role of Cdc20 homologues in Leishmania donovani cell cycle regulation.
To characterize the function and regulation of the L. donovani Cdc20 protein (LdCdc20p).

Main Methods:

Bioinformatic analysis to identify a Cdc20 homologue in the L. donovani genome.
Functional complementation assay using Saccharomyces cerevisiae lacking Cdc20.
Analysis of LdCdc20p expression patterns and its destruction motif.
Treatment of L. donovani promastigotes with proteasome inhibitors.

Main Results:

A functional Cdc20 homologue (LdCdc20p) was identified in L. donovani.
LdCdc20p successfully complemented the loss of Cdc20 in yeast, confirming its functionality.
LdCdc20p exhibits cyclic expression and possesses an active RXXL destruction motif.
Proteasome inhibition led to increased LdCdc20p levels in L. donovani promastigotes.

Conclusions:

Leishmania donovani employs a Cdc20 protein to regulate its cell cycle.
The Anaphase Promoting Complex/Cyclosome (APC/C) pathway, involving ubiquitin-dependent proteasomal degradation, is crucial for L. donovani cell cycle control.