This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Gerhard Wunderlich
University of Sao Paulo
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1724-0337
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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
This preprint is available for download as a PDF.
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryTable1.xlsx
ImageJ analysis of Westernblots in Figures 1 and 3
- SupplementaryTable2.xlsx
RNAseq results
- SupplementaryTable3RegulatedgeneswithTFmotifs.pdf
Differentially regulated transcripts with specific AP2 binding motifs
- SupplementaryTable4ProteomicAnalysis.pdf
PfAP2-O Coprecipitating proteins detected by mass spectrometry
- SupplementaryTable5RTPCRPrimers.xlsx
Sequences of primers used in RT.PCR analyses
- SupplDataFile1.docx
GLMM model for infection prevalence
- FigureS1.jpg
var transcription profile in parasites never submitted to silencing of PfAP2-O
- FigureS2.jpg
RNA seq analysis in PfAP2-O expressing and knocked-down parasites in biological triplicates
- FigureS3.jpg
Silver staining of purified protein complexes after antiHA immunoprecipitation
- FigureS4.jpg
Mean gametocytes number per 1000 RBC counted for each clone
- FigureS4a.jpg
Original Agarose gel image from the PCR reaction of Figure 1
- FigureS5.jpg
Original images from western blot results shown in Figures 1 and 4
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Gerhard Wunderlich
University of Sao Paulo
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1724-0337
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 10 Aug, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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
This preprint is available for download as a PDF.
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryTable1.xlsx
ImageJ analysis of Westernblots in Figures 1 and 3
- SupplementaryTable2.xlsx
RNAseq results
- SupplementaryTable3RegulatedgeneswithTFmotifs.pdf
Differentially regulated transcripts with specific AP2 binding motifs
- SupplementaryTable4ProteomicAnalysis.pdf
PfAP2-O Coprecipitating proteins detected by mass spectrometry
- SupplementaryTable5RTPCRPrimers.xlsx
Sequences of primers used in RT.PCR analyses
- SupplDataFile1.docx
GLMM model for infection prevalence
- FigureS1.jpg
var transcription profile in parasites never submitted to silencing of PfAP2-O
- FigureS2.jpg
RNA seq analysis in PfAP2-O expressing and knocked-down parasites in biological triplicates
- FigureS3.jpg
Silver staining of purified protein complexes after antiHA immunoprecipitation
- FigureS4.jpg
Mean gametocytes number per 1000 RBC counted for each clone
- FigureS4a.jpg
Original Agarose gel image from the PCR reaction of Figure 1
- FigureS5.jpg
Original images from western blot results shown in Figures 1 and 4
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