Related Experiment Video

Updated: Jun 2, 2026

Polysome Profiling in Leishmania, Human Cells and Mouse Testis
14:32

Polysome Profiling in Leishmania, Human Cells and Mouse Testis

Published on: April 8, 2018

Leishmania repression of host translation through mTOR cleavage is required for parasite survival and infection

Maritza Jaramillo1, Maria Adelaida Gomez, Ola Larsson

  • 1Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada.

Cell Host & Microbe
|April 20, 2011
PubMed

Insights

Leishmania parasites hijack host protein synthesis by cleaving mTOR, activating 4E-BPs to boost parasite growth. Inhibiting 4E-BPs reduces Leishmania infection, revealing a key survival strategy.

Area of Science:

  • Molecular parasitology
  • Host-pathogen interactions
  • Cellular signaling

Background:

  • Leishmania parasites manipulate host macrophages, but their impact on host protein synthesis remains unclear.
  • Understanding host protein synthesis regulation is crucial for deciphering parasite survival mechanisms.

Purpose of the Study:

  • To investigate how Leishmania infection affects host protein synthesis.
  • To identify host targets manipulated by Leishmania for proliferation.

Main Methods:

  • Analysis of mammalian/mechanistic target of rapamycin (mTOR) cleavage by Leishmania protease GP63.
  • Assessment of mTOR complex 1 (mTORC1) activity and 4E-BP1 phosphorylation.
  • Pharmacological (rapamycin) and genetic (4E-BP1/2 knockout) manipulation of 4E-BP1/2 pathways.
  • Evaluation of parasite load in vitro and Leishmania susceptibility in vivo.

Main Results:

  • Leishmania GP63 cleaves mTOR, inhibiting mTORC1 and activating 4E-BP1, which promotes parasite proliferation.
  • Rapamycin treatment significantly increases Leishmania replication by activating 4E-BPs.
  • Genetic deletion of 4E-BP1/2 reduces parasite load and Leishmania susceptibility in mice.
  • 4E-BP1/2 knockout mice exhibit enhanced type I interferon responses.

Conclusions:

  • Leishmania utilizes a survival strategy involving the activation of 4E-binding proteins (4E-BPs).
  • Host translational control via 4E-BPs is a critical target for Leishmania proliferation.
  • Targeting the 4E-BP pathway offers a potential therapeutic strategy against Leishmania infections.

More Related Videos

Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major08:17

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

Published on: October 28, 2022

Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites10:01

Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites

Published on: March 16, 2018

Related Concept Videos

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...
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...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Microbial Interactions: Parasitism01:22

Microbial Interactions: Parasitism

Parasitism is a form of microbial interaction in which parasitic microbes exploit a host organism for nutrients and shelter, often at the host's expense. Unlike mutualistic relationships, where both organisms benefit, parasitism benefits only the parasite and harms the host.Classification of ParasitesMicrobial parasites are broadly classified based on their location relative to the host.Ectoparasites remain on the host’s surface, such as the skin or outer tissues, drawing nutrients...
Malaria01:29

Malaria

Malaria pathogenesis in humans reflects a delicate interplay between parasite biology and host response. Clinical illness reflects a host’s immune response to the parasite’s asexual replication cycle, which is often asymptomatic in individuals with partial immunity. From the parasite's perspective, transmission between mosquito and human with minimal host pathology is evolutionarily advantageous. Among the six Plasmodium species infecting humans, P. falciparum and P. vivax dominate in global...
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life