An ApiAP2 transcription factor influencing virulence gene transcription and sexual development in Plasmodium falciparum
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 50-60 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 and other multigenic families. The temporary knockdown of PfAP2-O leads to a complete loss of var transcriptional memory and a decrease in cytoadherence. AP2-O-knocked down parasites exhibited also significant reductions in transmission through Anopheles mosquitoes. We propose that PfAP2-O is one of the major virulence gene transcriptional regulators and may, therefore, be exploited as an important target to disrupt severe malaria and block parasite transmission.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
ImageJ analysis of Westernblots in Figures 1 and 3
RNAseq results
Differentially regulated transcripts with specific AP2 binding motifs
PfAP2-O Coprecipitating proteins detected by mass spectrometry
Sequences of primers used in RT.PCR analyses
GLMM model for infection prevalence
var transcription profile in parasites never submitted to silencing of PfAP2-O
RNA seq analysis in PfAP2-O expressing and knocked-down parasites in biological triplicates
Silver staining of purified protein complexes after antiHA immunoprecipitation
Mean gametocytes number per 1000 RBC counted for each clone
Original Agarose gel image from the PCR reaction of Figure 1
Original images from western blot results shown in Figures 1 and 4
Posted 10 Aug, 2020
An ApiAP2 transcription factor influencing virulence gene transcription and sexual development in Plasmodium falciparum
Posted 10 Aug, 2020
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 50-60 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 and other multigenic families. The temporary knockdown of PfAP2-O leads to a complete loss of var transcriptional memory and a decrease in cytoadherence. AP2-O-knocked down parasites exhibited also significant reductions in transmission through Anopheles mosquitoes. We propose that PfAP2-O is one of the major virulence gene transcriptional regulators and may, therefore, be exploited as an important target to disrupt severe malaria and block parasite transmission.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.