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Related Concept Videos

Leishmaniasis01:30

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 Agents01:21

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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Related Experiment Video

Updated: May 29, 2026

Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
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Using machine learning to dissect host kinases required for Leishmania internalization and development.

Ling Wei1, Umaru Barrie2,3, Gina M Aloisio2,3

  • 1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, United States.

Biorxiv : the Preprint Server for Biology
|May 27, 2024
PubMed
Summary

This study identifies host kinases regulating Leishmania parasite uptake and survival. Novel kinases were discovered, suggesting complex host kinase networks are crucial for Leishmania infection.

Keywords:
Fc receptorLeishmaniacomplement receptorkinase regressionphagocytosisphosphosignaling

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Area of Science:

  • Immunology
  • Cell Biology
  • Parasitology

Background:

  • The Leishmania parasite alternates between sandfly promastigotes and mammalian amastigotes.
  • Phagocyte uptake of promastigotes initiates infection, requiring amastigote survival within phagolysosomes.

Purpose of the Study:

  • To identify host kinase regulators of Leishmania promastigote and amastigote uptake and survival in macrophages.
  • To differentiate parasite uptake mechanisms from generalized phagocytosis.

Main Methods:

  • An image-based kinase regression screen using 38 kinase inhibitors.
  • Targeting inert beads to complement receptor 3 (CR3) or Fcγ receptors (FcR) as controls.
  • Analyzing host kinase regulation of Leishmania amazonensis uptake and intracellular survival.

Main Results:

  • Identified known kinases (Src family kinases, Abl family kinases, SYK) and novel kinases regulating Leishmania uptake.
  • Predicted host kinases involved in promastigote-to-amastigote conversion and amastigote survival.
  • Discovered kinases preferentially regulating parasite uptake over bead uptake, suggesting distinct mechanisms.

Conclusions:

  • Multiple interconnected host kinase networks are essential throughout Leishmania infection.
  • Kinase requirements vary based on receptor binding and parasite life cycle stage.
  • Findings provide a resource for studying host-pathogen interactions and kinase roles in Leishmania.