Summary of Study ST002698
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002698 |
| Study Title | Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites |
| Study Type | Biomedical research |
| Study Summary | We found that host inflammation altered the plasma environment surrounding Plasmodium falciparum parasites in vivo, and that this altered plasma environment contained inhibitory factors that directly impaired maturation of early trophozoite stages. We demonstrated with LPS-conditioning that systemic host inflammation alone, in the absence of confounding factors such as ongoing infection, slowed the rate at which parasites transited from one generation of RBC to the next. While this is consistent with the idea that host inflammatory responses can impair parasite maturation, other TLR agonists, CpG and Poly I:C, did not elicit such a response. Metabolomics also identified 1-methylhypoxanthine as elevated in both LPS conditioned and acutely-infected plasma. Plasmodium survival depends on host hypoxanthine, inosine and xanthine for purine synthesis. 1-Methylhypoxanthine can bind effectively to and possibly limit the action of hypoxanthine-guanine phosphoribosyl transferase (HGPRTase)25, an enzyme critical for purine synthesis. Interestingly, hypoxanthine, inosine and xanthine were also all reduced in the plasma of LPS-conditioned and acutely infected mice supporting the possibility that inhibition of purine synthesis by 1-methylhypoxanthine might have been partly aided by the lack of substrates for this pathway. |
| 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 |
| ollie.skinner@unimelb.edu.au | |
| Phone | +61 424088268 |
| Submit Date | 2023-04-29 |
| Num Groups | 5 |
| Total Subjects | 25 |
| Num Males | NA |
| Num Females | NA |
| Study Comments | Malaria parasite cultures treatments: CpG, LPS, PbA, PIC, Saline |
| Publications | Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-06-26 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Sample Preparation:
| Sampleprep ID: | SP002807 |
| Sampleprep Summary: | Two independent experiments were conducted, each with 6 mice per treatment group. Ice-cold butanol/methanol (1:1) containing 50 µg/mL antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT) was added to each plasma sample, as well as a pooled quality control (QC) sample at 10x volume. Samples were vortexed for 10 seconds then snap frozen on dry ice. Thawed samples were sonicated for 15 minutes on ice, stored for 2 hours at -30°C, and then centrifuged for 15 minutes at 16,000×g (4°C). Supernatant was collected, aliquoted, dried down using a vacuum concentrator and stored at -80°C until LC/MS analysis. |
| Processing Storage Conditions: | 4℃ |
| Extraction Method: | MeOH/BuOH (1:1) |
| Extract Storage: | -80℃ |
| Sample Resuspension: | NA |
| Sample Derivatization: | NA |
