Distinct metabolic perturbations associated with pediatric Plasmodium falciparum malaria during Intra-erythrocytic development stage
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156791 | GEO | 2021/04/26
REPOSITORIES: GEO
Similar Datasets
Project description:Distinct metabolic perturbations associated with pediatric Plasmodium falciparum malaria during Intra-erythrocytic development stage
| PRJNA659032 | ENA
Project description:The microarray experiments were carried out using a long oligonucleotide DNA microarray that represent all 5363 P. falciparum genes with one oligonucleotide per 1.9kb of coding sequence on average (Hu et al. 2007). Total 247 microarray experiments were carried out including 29-drug treatment time courses with 20 compounds and corresponding untreated controls from different drug or inhibitor treatment. Data of each drug/inhibitor experiment were normalized using a linear normalization and background filtering as implemented by the NOMAD database (http://derisilab.ucsf.edu).
2009-12-16 | GSE19468 | GEO
Project description:Despite substantial progress in the control of Plasmodium falciparum infection due to the widespread deployment of insecticide-treated bed nets and artemisinin combination therapies, malaria remains a prolific killer, with over half a million deaths estimated to have occurred in 2013 alone. Recent evidence of the development of resistance to treatments in both parasites and their mosquito vectors has underscored the need for a vaccine. Here, we use a mathematical model of the within-host dynamics of P. falciparum infection, fit to data from controlled human malaria infection clinical trials, to predict the efficacy of co-administering the two most promising subunit vaccines, RTS,S/AS01 and ChAd63-MVA ME-TRAP. We conclude that currently available technologies could be combined to induce very high levels of sterile efficacy, even in immune-naive individuals.
| S-EPMC4674243 | biostudies-literature
Project description:The phospholipid and fatty acid compositions of the host infected erythrocyte plasma membrane (IEPM) have been determined for erythrocytes infected with the human malaria parasite Plasmodium falciparum. IEPM were prepared by selective lysis of the host erythrocyte (but not of the parasite membranes) with 0.1% saponin, followed by differential centrifugation. The purity of the IEPM was determined by measuring the membrane-specific enzyme markers acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by immunoelectron microscopy using monoclonal antibodies specific for human erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma membrane preparation was free from contamination by parasite membranes. During intra-erythrocytic development of the parasite, the phospholipid composition of the erythrocyte membrane was strikingly altered. IEPM contained more phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus 0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected erythrocytes. Similar alterations in phospholipid composition were determined for erythrocyte membranes of parasitized cells isolated by an alternative method utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty acid compositions of the major phospholipids in IEPM were determined by g.l.c. The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar to that in purified parasites (107.5 versus 98.5). Large increases in palmitic acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to 24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%) and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of infection. The fatty acid profiles of individual phospholipid classes from IEPM resembled in many instances the fatty acid profiles of parasite phospholipids rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum-infected erythrocytes (trophozoite stage) revealed that, during intra-erythrocytic maturation of the parasite, the host erythrocyte phospholipid composition was markedly refashioned. These alterations were not dependent on the method used to isolate the IEPM, with similar results obtained using either a saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have negligible lipid synthesis and metabolism, these alterations must occur as a result of parasite-directed metabolism of erythrocyte lipids and/or trafficking of lipids between the parasite and erythrocyte membranes.
| S-EPMC1149929 | biostudies-other
Project description:The microarray experiments were carried out using a long oligonucleotide DNA microarray that represent all 5363 P. falciparum genes with one oligonucleotide per 1.9kb of coding sequence on average (Hu et al. 2007). Total 247 microarray experiments were carried out including 29-drug treatment time courses with 20 compounds and corresponding untreated controls from different drug or inhibitor treatment. Data of each drug/inhibitor experiment were normalized using a linear normalization and background filtering as implemented by the NOMAD database (http://derisilab.ucsf.edu). Time-series sampling and experiments with synchronized ex vivo culturing parasites. Each experiment has treatment and controls, and starts at a specific time of post invasion. For an example of quinine treatment, the treatments start from late ring stage through trophozoite stage of the parasites. First, IC50 is determined by drug assay with synchronized parasites (5% parasiteomia and 2% RBC). Second, synchronized parasite cultures are splitted into 12 flasks (75ml culture/flask) for a 6 time-point time-series experiment. 6 flasks are treated with quinine (final concentration is IC50) and 6 flasks are negative controls. 1,2,4,6,8 and 10 hrs after the treatment, parasites in each flask were harvested for total RNA isolation and microarray hybridizaiton.
2010-05-18 | E-GEOD-19468 | biostudies-arrayexpress
Project description:Malaria pathogenesis, encompassing parasite invasion, egress, and antigenic variation, relies on the coordinated activity of numerous proteins, yet their molecular regulatory mechanisms remain poorly understood. Here, we define the role of PfAP2-V, a critical AP2 transcription factor in Plasmodium falciparum, during intra-erythrocytic developmental cycle. PfAP2-V displayed two distinct peaks of expression and was critical for parasite proliferation, invasion, and the regulation of virulence-associated genes. Inducible knockdown of PfAP2-V reduced parasitemia by blocking trophozoite development, which was associated with downregulated phosphorylation of virulence-associated proteins. Furthermore, PfAP2-V knockdown reduced PfEMP1 expression, impairing the adhesion of infected red blood cells to endothelial receptors. Genome-wide chromosome conformation capture and chromatin immunoprecipitation sequencing analyses revealed that PfAP2-V knockdown altered chromatin interactions and accessibility, disrupting the regulation of antigenic variant genes. These findings establish PfAP2-V as a key transcriptional regulator at distinct stages of the intra-erythrocytic cycle.
2025-03-25 | GSE288146 | GEO
Project description:The regulation of immune cell responses to infection is a complex process that involves various molecular mechanisms, including epigenetic regulation. DNA methylation has been shown to play central roles in regulating gene expression and modulating cell response during infection. However, the nature and extent to which DNA methylation is involved in the host immune response in human malaria remains unknown. Here, we present a longitudinal study investigating the temporal dynamics of genome-wide in vivo DNA methylation profiles using 189 MethylationEPIC 850K profiles from 66 children in Burkina Faso, West Africa, sampled three times: before infection, during symptomatic parasitemia, and after malaria treatment. The results revealed major changes in the DNA methylation profiles of children in response to both Plasmodium falciparum infection and malaria treatment, with widespread hypomethylation of CpGs upon infection (82% of 6.8K differentially methylated regions). We document a remarkable reversal of CpG methylation profiles upon treatment to pre-infection states. These changes implicate divergence in core immune processes, including the regulation of lymphocyte, neutrophil, and myeloid leukocyte function. Integrative DNA methylation-mRNA analysis of a top differentially methylated region overlapping the pro-inflammatory gene TNF implicates DNA methylation of TNF cis regulatory elements in the molecular mechanisms of TNF regulation in human malaria. Our results highlight a central role of epigenetic regulation in mounting the host immune response to Plasmodium falciparum infection and in response to malaria treatment.
2023-06-08 | GSE230850 | GEO
Project description:The objective of this study is to characterize the overall transcriptome of P. falciparum NF54 derived from a controlled-human malaria infection (CHMI) study. Healthy, immunologically naïve human volunteers were infected intradermally or intravenously with different dosages of Plasmodium falciparum sporozoites (Sanaria® PfSPZ Challenge). Parasites were isolated from these volunteers and subjected to a range of in vitro culture generation prior to RNA collection.
2019-08-21 | GSE136076 | GEO
Project description:The malaria parasite Plasmodium falciparum replicates via schizogony: a fundamentally unusual type of cell cycle involving asynchronous replication of multiple nuclei within the same cytoplasm. It also has one of the most A/T-biased genomes ever sequenced. Here, we present the first comprehensive study of the specification and activation of DNA replication origins during Plasmodium schizogony. Potential replication origins were found to be abundant, with ORC1-binding sites detected every ~800 bp throughout the genome. They had no motif enrichment, but were biased towards areas of higher G/C content. Origin activation was then measured at single-molecule resolution via DNAscent technology, and was much less dense than ORC1-binding sites, with origins activated preferentially in areas of low transcriptional activity. Consistently, replication forks moved slowest through the most highly transcribed genes, suggesting that conflicts between transcription and origin firing inhibit efficient replication, and that P. falciparum has evolved its S-phase to minimise such conflicts.
2023-01-30 | GSE208757 | GEO
Project description:Survey of transcriptional activity across 22.6% of the P. falciparum strain 3D7 genome. 872 protein coding genes and 60 putative P. falciparum lncRNAs identified under developmental regulation during the parasite's pathogenic human blood stage.
2011-03-16 | GSE27937 | GEO