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| Status |
Public on Sep 01, 2022 |
| Title |
Adaptation of Plasmodium falciparum to growth in medium lacking a lipids supplement is associated with mutations in the pfndh2 gene |
| Organism |
Plasmodium falciparum |
| Experiment type |
Expression profiling by array
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| Summary |
The complex life cycle of the malaria parasite Plasmodium falciparum involves many different environments. Additionally, the parasite encounters fluctuating conditions within the same niche. For example, in the human blood parasites face variability in the host’s immune response, presence of antimalarial drugs or availability of nutrients, among others. Bet-hedging adaptive strategies, which involve population heterogeneity that precedes changes in the environment, play an important role in the adaptation of P. falciparum asexual blood stages to fluctuations in their environment. This is linked to clonally variant expression, regulated at the epigenetic level, of a large number of malarial genes. However, currently there are very few examples of fluctuation conditions to which adaptation by changes in the expression of clonally variant genes has been established. Here we studied the adaptation of P. falciparum cultures to grow in the absence of an external source of lipids. In three independent adaptation experiments, cultures were able to adapt to grow without lipids in the culture medium and this was linked to acquisition of deletions or non-sense mutations in the pfndh2 gene, a component of the mitochondrial electron transport chain. In contrast, full transcriptome analysis did not provide evidence for a role for bet-hedging strategies in the adaptation of parasites to grow in lipid-free medium. Therefore, adaptation to this type of stress involved metabolic rewiring achieved by inactivation of a gene involved the mitochondrial respiratory chains.
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| Overall design |
Time-course transcriptomic analysis of 3D7-A parasites from two independent selections (Selection 2 and Selection 3) in which parasites (3D7-A-LF) were selected with lipid-free media supplemented with 0.5% bovine serum albumin (BSA) for 30 to 60 days and maintained in parallel with control parasites (3D7-A-Ctrl) that were in fully-supplemented 0.5% AlbuMAX II medium. Parasites were tightly synchronized to a 5 h age window by the means of a Percoll purification followed by a sorbitol lysis 5 h later. After the Percoll, 3D7-A-LF parasites were separated into two conditions: LF0 that was always maintained in lipid-free 0.5% BSA supplemented media and LFCM that was switched to 0.5% AlbuMAX II supplemented media for the duration of this experiment. 3D7-A-Ctrl parasites were always kept in 0.5% AlbuMAX II supplemented media. Samples for transcriptomic analysis were collected every 8 h at five different time points (8-13 hpi, 16-21 hpi, 24-29 hpi, 32-37 hpi and 40-45 hpi). The reference pool consisted of RNA from 3D7-A cultures throughout the asexual blood cycle. Total RNA was harvested using the Trizol method. A total number of 30 individual samples were analysed using the microarray design AMADID-085763 (GEO ID: GPL26985).
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| Contributor(s) |
Pickford A, Michel-Todó L, Cortés A |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Sep 06, 2021 |
| Last update date |
Sep 03, 2022 |
| Contact name |
Anastasia Pickford |
| E-mail(s) |
anastasia.pickford@isglobal.org
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| Organization name |
ISGlobal
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| Lab |
Malaria Epigenetics
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| Street address |
Carrer Rosselló 153
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| City |
Barcelona |
| State/province |
Barcelona |
| ZIP/Postal code |
08036 |
| Country |
Spain |
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| Platforms (1) |
| GPL26985 |
Agilent-085763 Pfalciparum15KArray_Sept18 |
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| Samples (30)
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| GSM5558788 |
Selection 2, 3D7-A-Ctrl parasites, 8-13hpi |
| GSM5558789 |
Selection 2, 3D7-A-Ctrl parasites, 16-21hpi |
| GSM5558790 |
Selection 2, 3D7-A-Ctrl parasites, 24-29hpi |
| GSM5558791 |
Selection 2, 3D7-A-Ctrl parasites, 32-37hpi |
| GSM5558792 |
Selection 2, 3D7-A-Ctrl parasites, 40-45hpi |
| GSM5558793 |
Selection 2, 3D7-A-LF parasites, LF0 condition, 8-13hpi |
| GSM5558794 |
Selection 2, 3D7-A-LF parasites, LF0 condition, 16-21hpi |
| GSM5558795 |
Selection 2, 3D7-A-LF parasites, LF0 condition, 24-29hpi |
| GSM5558796 |
Selection 2, 3D7-A-LF parasites, LF0 condition, 32-37hpi |
| GSM5558797 |
Selection 2, 3D7-A-LF parasites, LF0 condition, 40-45hpi |
| GSM5558798 |
Selection 2, 3D7-A-LF parasites, LFCM condition, 8-13hpi |
| GSM5558799 |
Selection 2, 3D7-A-LF parasites, LFCM condition, 16-21hpi |
| GSM5558800 |
Selection 2, 3D7-A-LF parasites, LFCM condition, 24-29hpi |
| GSM5558801 |
Selection 2, 3D7-A-LF parasites, LFCM condition, 32-37hpi |
| GSM5558802 |
Selection 2, 3D7-A-LF parasites, LFCM condition, 40-45hpi |
| GSM5558803 |
Selection 3, 3D7-A-Ctrl parasites, 8-13hpi |
| GSM5558804 |
Selection 3, 3D7-A-Ctrl parasites, 16-21hpi |
| GSM5558805 |
Selection 3, 3D7-A-Ctrl parasites, 24-29hpi |
| GSM5558806 |
Selection 3, 3D7-A-Ctrl parasites, 32-37hpi |
| GSM5558807 |
Selection 3, 3D7-A-Ctrl parasites, 40-45hpi |
| GSM5558808 |
Selection 3, 3D7-A-LF parasites, LF0 condition, 8-13hpi |
| GSM5558809 |
Selection 3, 3D7-A-LF parasites, LF0 condition, 16-21hpi |
| GSM5558810 |
Selection 3, 3D7-A-LF parasites, LF0 condition, 24-29hpi |
| GSM5558811 |
Selection 3, 3D7-A-LF parasites, LF0 condition, 32-37hpi |
| GSM5558812 |
Selection 3, 3D7-A-LF parasites, LF0 condition, 40-45hpi |
| GSM5558813 |
Selection 3, 3D7-A-LF parasites, LFCM condition, 8-13hpi |
| GSM5558814 |
Selection 3, 3D7-A-LF parasites, LFCM condition, 16-21hpi |
| GSM5558815 |
Selection 3, 3D7-A-LF parasites, LFCM condition, 24-29hpi |
| GSM5558816 |
Selection 3, 3D7-A-LF parasites, LFCM condition, 32-37hpi |
| GSM5558817 |
Selection 3, 3D7-A-LF parasites, LFCM condition, 40-45hpi |
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| Relations |
| BioProject |
PRJNA761122 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE183526_RAW.tar |
47.8 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE183526_processed_data.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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