ArticleCellular microbiology2018
Leishmania parasitophorous vacuole membranes display phosphoinositides that create conditions for continuous Akt activation and a target for miltefosine in Leishmania infections.
Article in Cellular microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Systemic Review of Clot Retraction Modulators.International journal of molecular sciences · 2023Pooled it
- Miltefosine and emerging Leishmania (Mundinia) in Southeast Asia: Molecular insights, therapeutic challenges, and future strategic implementation.PLoS neglected tropical diseases · 2026Review
- PI3K/AKT signaling in parasites and parasite diseases: Role and therapeutic potential.Virulence · 2025Review
- A non-canonical activation of the host's ESCRT machinery is required for the scission of parasitophorous vacuoles and the replication of Leishmania donovani.PLoS pathogens · 2025Article
- Can letrozole be repurposed for the treatment of visceral leishmaniasis?Antimicrobial agents and chemotherapy · 2024Article
- Acarbose presents in vitro and in vivo antileishmanial activity against Leishmania infantum and is a promising therapeutic candidate against visceral leishmaniasis.Medical microbiology and immunology · 2021Article
- Identification of Metabolically QuiescentmBio · 2021Article
- Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective.Microorganisms · 2021Review
- Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts.PLoS pathogens · 2020Article
- TheThe Yale journal of biology and medicine · 2019Review
- Leishmania donovani Lipophosphoglycan Increases Macrophage-Dependent Chemotaxis of CXCR6-Expressing Cells via CXCL16 Induction.Infection and immunity · 2019Article
- Miransertib (ARQ 092), an orally-available, selective Akt inhibitor is effective against Leishmania.PloS one · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Miltefosine is an important drug for the treatment of leishmaniasis; however, its mechanism of action is still poorly understood. In these studies, we tested the hypothesis that like in cancer cells, miltefosine's efficacy in leishmaniasis is due to its inhibition of Akt activation in host cells. We show using pharmacologic agents that block Akt activation by different mechanisms and also using an inducible knockdown approach that miltefosine loses its efficacy when its access to Akt1 is limited. Interestingly, limitation of Akt activation results in clearance of established Leishmania infections. We then show, using fluorophore-tagged probes that bind to phosphoinositides, that Leishmania parasitophorous vacuole membranes (LPVMs) display the relevant phosphoinositides to which Akt can be recruited and activated continuously. Taken together, we propose that the acquisition of PI(4) P and the display of PI (3,4)P2 on LPVMs initiate the machinery that supports continuous Akt activation and sensitivity to miltefosine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.