Dataset Information

Adaptation of Plasmodium falciparum to growth in medium lacking a lipids supplement is associated with mutations in the pfndh2 gene

ABSTRACT: 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.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE183526 | GEO | 2022/09/01

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterised by the accumulation of infected erythrocytes in the microvasculature of the brain, due to parasite adhesins on the surface of infected erythrocytes binding to human receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We used the Human Brain Endothelial Cell line HBEC-5i to identify the malaria parasite ligands responsible for binding to human brain endothelial cells. Three P. falciparum strains (HB3, 3D7 and IT/FCR3) were selected for binding to HBEC5i and the whole transcriptome of selected and unselected parasites was analysed using a variant surface antigen-supplemented microarray chip. After selection, the only highly upregulated genes were a subset of group A-like var genes (HB3var3, 3D7_PFD0020c, ITvar7 and ITvar19), that showed 11 to >100-fold higher transcription levels in selected parasites. These genes are highly diverse in sequence, but do however show strong similarities in PfEMP1 architecture. Antibodies raised to the HB3var3 variant recognized the surface of infected erythrocytes and abolished the binding of infected erythrocytes to brain endothelial cells. The subset of Group A PfEMP1 variants identified here provides a new target for interventions to treat or prevent cerebral malaria. Unselected Plasmodium falciparum parasites (Uns) only poorly cytoadhere to human brain endothelial cells (HBEC-5i). Plasmodium falciparum HB3, 3D7 and IT/FCR3 strains were selected for binding to HBEC-5i (HB3-HBEC1, HB3-HBEC2, HB3-HBEC-TNF, 3D7-HBEC and IT-HBEC). HBEC-selected and unselected cultures were tightly synchronised before a timecourse experiment was performed. 6 samples, named time points 1 to 6, were taken every 8 hours. 12μg of RNA from the unselected parasites (HB3-Uns, 3D7-Uns or IT-Uns) at each of the 6 time points was combined together to form the reference pool. The pool and 12μg of each individual time point sample from both selected and unselectedparasites were then used for cDNA synthesis. For HB3-HBEC1 (pilot experiment), each HB3-HBEC1 time point (pilot experiment) was hybridised directly with HB3-Uns1 time points. For microarray hybridizations, each cDNA sample was coupled to Cy5 (red dye) while Cy3 (green dye) was added to the pool. Cy5-labelled time point samples were mixed with the same amount of Cy3-labelled pool sample. The solution was loaded on a microarray slide and hybridized for 14–16 h.

Dataset Information

Adaptation of Plasmodium falciparum to growth in medium lacking a lipids supplement is associated with mutations in the pfndh2 gene

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure