Summary of project PR002327
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002327. The data can be accessed directly via it's Project DOI: 10.21228/M8V24V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002327 |
| Project DOI: | doi: 10.21228/M8V24V |
| Project Title: | A Metabolite-Based Resistance Mechanism Against Malaria |
| Project Summary: | Jaundice is a common clinical presentation of Plasmodium (P.) falciparum malaria, arising from the accumulation of circulating bilirubin. Whether the active production of this lipophilic yellow pigment by biliverdin reductase A (BVRA) represents an adaptive or maladaptive response to Plasmodium infection is not understood. Here we found that the transition of P. falciparum infection from asymptomatic towards symptomatic malaria was associated with a >10-fold reduction in the ratio of circulating unconjugated bilirubin over parasite burden. Genetic deletion of Blvra in mice suppressed bilirubin production and precipitated malaria mortality, owed to higher parasite burden and virulence. Inhibition of bilirubin conjugation by the repression of hepatic UDP glucuronosyltransferase family 1 member A1 (UGT1A1), increased the levels of circulating unconjugated bilirubin and prevented malaria mortality. Unconjugated bilirubin targeted P. falciparum directly inside red blood cells (RBC) to suppress mitochondrion pyrimidine synthesis and inhibit the formation of hemozoin crystals, compromising the parasite´s food vacuole´s capacity to detoxify heme and extract essential amino acids (AA) from hemoglobin. In conclusion, jaundice represents an evolutionary conserved metabolic response to Plasmodium spp. infection that limits malaria severity. |
| Institute: | European Molecular Biology Laboratory |
| Department: | EMBL Heidelberg |
| Last Name: | Drotleff |
| First Name: | Bernhard |
| Address: | Meyerhofstr. 1, Heidelberg, BW, 69117, Germany |
| Email: | bernhard.drotleff@embl.de |
| Phone: | none |
| Publications: | in preparation |
| Contributors: | Ana Figueiredo, Sonia Trikha Rastogi, Susana Ramos, Fátima Nogueira, Katherine De Villiers, António G. Gonçalves de Sousa, Lasse Votborg-Novél, Cäcilie von Wedel, Pinkus Tober-Lau, Elisa Jentho, Sara Pagnotta, Miguel Mesquita, Silvia Cardoso, Giulia Bortolussi, Andres Munro, Erin M. Tranfield, Jessica Thibaud, Denise Duarte, Ana Laura Sousa, Sandra N. Pinto, Jamil Kitoko, Ghyslain Mombo-Ngoma, Johannes Mischlinger, Sini Junttila, Marta Alenquer, Maria João Amorim, Chirag Vasavda, Piter J. Bosma, Sara Violante, Bernhard Drotleff, Tiago Paixão, Silvia Portugal, Florian Kurth, Laura L. Elo, Bindu Paul, Rui Martins & Miguel P. Soares |
Summary of all studies in project PR002327
| Study ID | Study Title | Species | Institute | Analysis (* : Contains Untargted data) |
Release Date | Version | Samples | Download (* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003741 | A Metabolite-Based Resistance Mechanism Against Malaria | Homo sapiens | European Molecular Biology Laboratory | MS | 2025-03-24 | 1 | 112 | Uploaded data (9.5G)* |
