Summary of project PR001670
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 PR001670. The data can be accessed directly via it's Project DOI: 10.21228/M8V14H This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001670 |
| Project DOI: | doi: 10.21228/M8V14H |
| Project Title: | Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites (University of Melbourne) |
| Project Type: | Untargeted LCMS metabolomics |
| Project Summary: | Maturation rates of malaria parasites within red blood cells (RBC) can be influenced by host nutrient status and circadian rhythm; whether host inflammatory responses can also influence maturation remains less clear. Here, we observed that systemic host inflammation induced in mice by an innate immune stimulus, lipopolysaccharide (LPS), or by ongoing acute Plasmodium infection, slowed the progression of a single cohort of parasites from one generation of RBC to the next. Importantly, plasma from LPS-conditioned or acutely-infected mice directly inhibited parasite maturation during in vitro culture, which was not rescued by supplementation, suggesting the emergence of inhibitory factors in plasma. Metabolomic assessments confirmed substantial alterations to the plasma of LPS-conditioned and acutely-infected mice, and identified a small number of candidate inhibitory metabolites, some of which could interfere with Plasmodium purine synthesis. Finally, we confirmed rapid parasite responses to systemic host inflammation in vivo using parasite scRNA-seq, noting broad impairment in transcriptional activity and translational capacity specifically in trophozoites, but not rings or schizonts. Thus, we provide evidence that systemic host inflammation rapidly triggered transcriptional alterations in circulating blood-stage Plasmodium trophozoites, and predict candidate inhibitory metabolites in the plasma that may impair parasite maturation in vivo. |
| Institute: | Peter Doherty Institute for Infection and Immunity |
| Department: | Department of Microbiology and Immunology |
| Laboratory: | Ashraful Haque lab |
| Last Name: | Skinner |
| First Name: | Oliver |
| Address: | 792 Elizabeth Street, The University of Melbourne, Victoria 3000 Australia |
| Email: | ollie.skinner@unimelb.edu.au |
| Phone: | +61 424088268 |
| Publications: | Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites |
| Contributors: | Lianne I.M. Lansink, Oliver P. Skinner, Jessica A. Engel, Hyun Jae Lee, Megan S.F. Soon, Cameron G. Williams, Arya SheelaNair, Clara P.S. Pernold, Pawat Laohamonthonkul, Jasmin Akter, Thomas Stoll, Michelle Hill, Arthur M. Talman, Andrew Russell, Mara Lawniczak, Xiaoxiao Jia, Brendon Chua, Dovile Anderson, Darren J. Creek, Miles P. Davenport, David S. Khoury, Ashraful Haque |
Summary of all studies in project PR001670
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002698 | Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites | Plasmodium berghei | Peter Doherty Institute for Infection and Immunity | MS | 2023-06-26 | 1 | 31 | Uploaded data (3.2G)* |
