Generation of inositol polyphosphates through a phospholipase C-independent pathway involving carbohydrate and sphingolipid metabolism in <i>Trypanosoma cruzi</i>
Millions of people are infected with <i>Trypanosoma cruzi,</i> and the current treatment is not satisfactory. Inositol pyrophosphates have been established as important signaling molecules. Our work demonstrates the presence of a phospholipase C-independent pathway for the synthesis of inositol pyrophosphates in <i>T. cruzi</i>. Furthermore, we demonstrate that this pathway starts with the synthesis of inositol monophosphates from glucose 6-phosphate or from inositol phosphoceramide, linking it to carbohydrate and sphingolipid metabolism. The essentiality of the pathway for the survival of <i>T. cruzi</i> infective stages makes it an ideal drug target for treating American trypanosomiasis.
Authors
- Roberto Docampo (ORCID: https://orcid.org/0000-0003-4229-8784)
- Mayara S. Bertolini (ORCID: https://orcid.org/0000-0002-2489-434X)
- Logan P. Crowe (ORCID: https://orcid.org/0000-0002-8378-7499)
- Henning Jacob Jessen (ORCID: https://orcid.org/0000-0002-1025-9484)
- Brian S. Mantilla (ORCID: https://orcid.org/0000-0001-7839-1222)
- Danye Qiu (ORCID: https://orcid.org/0000-0003-2197-3218)
- Sabrina E. Cline
- Miguel Ángel Chiurillo (ORCID: https://orcid.org/0000-0002-5581-9027)
- Adolfo Saiardi (ORCID: https://orcid.org/0000-0002-4351-0081)
- Aharon Eidex
Institutions
- University of Leeds (GB)
- University of Freiburg (DE)
- University of Georgia (US)
- MRC Laboratory for Molecular Cell Biology (GB)
- University College London (GB)
- University of Cincinnati (US)
- Medical Research Council (GB)
Publication Details
- Journal
- mBio
- Published
- 2025-04-04
- DOI
- https://doi.org/10.1128/mbio.03318-24
- Citations
- 1
- Primary Topic
- Trypanosoma species research and implications
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- American Heart Association
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Medical Research Council Canada
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases