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Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE135006 | GEO | 2020/06/10

REPOSITORIES: GEO

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Conditional expression of PfAP2-G for controlled massive sexual conversion in <i>Plasmodium falciparum</i>.

Project description:Malaria transmission requires that some asexual parasites convert into sexual forms termed gametocytes. The initial stages of sexual development, including sexually committed schizonts and sexual rings, remain poorly characterized, mainly because they are morphologically identical to their asexual counterparts and only a small subset of parasites undergo sexual development. Here, we describe a system for controlled sexual conversion in the human malaria parasite Plasmodium falciparum, based on conditional expression of the PfAP2-G transcription factor. Using this system, ~90 percent of the parasites converted into sexual forms upon induction, enabling the characterization of committed and early sexual stages without further purification. We characterized sexually committed schizonts and sexual rings at the transcriptomic and phenotypic levels, which revealed down-regulation of genes involved in solute transport upon sexual commitment, among other findings. The new inducible lines will facilitate the study of early sexual stages at additional levels, including multiomic characterization and drug susceptibility assays.

| S-EPMC7286680 | biostudies-literature

Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum [array]

Project description:Malaria transmission requires the conversion of some asexual parasites into sexual forms termed gametocytes. The initial stages of sexual development, including sexually-committed schizonts and sexual rings, remain poorly characterized, in part because only a subset of parasites undergo sexual development and they are morphologically identical to their asexual counterparts. Here we present a system based on conditional expression of PfAP2-G, the master regulator of sexual conversion, for controlled sexual induction. Induction resulted in ~90% sexual conversion, which enables the characterization of early sexual stages without further purification. Transcriptomic analysis identified the alterations that follow pfap2-g activation, including identification of genes that are down-regulated. We also show that the inducible system enables the characterization of committed stages at the phenotypic level. Altogether, the inducible lines will facilitate the study of the initial stages of sexual development, which is important for the development of new strategies to stop malaria transmission.

2020-06-10 | GSE135005 | GEO

Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum. [ChIP-Seq]

2020-06-10 | GSE135002 | GEO

Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum

Project description:Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum

| PRJNA557124 | ENA

Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum [array]

Project description:Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum [array]

| PRJNA557126 | ENA

Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum. [ChIP-Seq]

Project description:Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum. [ChIP-Seq]

| PRJNA557120 | ENA

Roles of PfAP2-EXP2 in Plasmodium falciparum blood-stage development

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-02 | GSE180438 | GEO

The Transcription Factor PfAP2-O Influences Virulence Gene Transcription and Sexual Development in <i>Plasmodium falciparum</i>.

Project description:The human malaria parasite Plasmodium falciparum expresses variant PfEMP1 proteins on the infected erythrocyte, which function as ligands for endothelial receptors in capillary vessels, leading to erythrocyte sequestration and severe malaria. The factors that orchestrate the mono-allelic expression of the 45-90 PfEMP1-encoding var genes within each parasite genome are still not fully identified. Here, we show that the transcription factor PfAP2-O influences the transcription of var genes. The temporary knockdown of PfAP2-O leads to a complete loss of var transcriptional memory and a decrease in cytoadherence in CD36 adherent parasites. AP2-O-knocked-down parasites exhibited also significant reductions in transmission through Anopheles mosquitoes. We propose that PfAP2-O is, beside its role in transmission stages, also one of the virulence gene transcriptional regulators and may therefore be exploited as an important target to disrupt severe malaria and block parasite transmission.

| S-EPMC8275450 | biostudies-literature

Plasmodium falciparum infection

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-02-15 | E-GEOD-35936 | biostudies-arrayexpress

PfAP2-O Influences Virulence Gene Transcription and Sexual Development in Plasmodium falciparum

Project description:The project examined the function of the putative transcription factor PfAP2-O from Plasmodium falciparum. This factor besides an essential function in sexual stages also influences variant, virulence associated genes. In a pull down analysis, HA-tagged PfAP2-O was immunoprecipitated and proteins assoaciated were analysed and three differentially appearing protein bands were analysed.

2021-06-28 | PXD026237 | Pride

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