AUTHOR=Cubillos Eliana F. G. , Prata Isadora Oliveira , Fotoran Wesley Luzetti , Ranford-Cartwright Lisa , Wunderlich Gerhard 

TITLE=The Transcription Factor PfAP2-O Influences Virulence Gene Transcription and Sexual Development in Plasmodium falciparum

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.669088

DOI=10.3389/fcimb.2021.669088

ISSN=2235-2988

ABSTRACT=<p>The human malaria parasite <italic>Plasmodium falciparum</italic> 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 <italic>var</italic> genes within each parasite genome are still not fully identified. Here, we show that the transcription factor PfAP2-O influences the transcription of <italic>var</italic> genes. The temporary knockdown of PfAP2-O leads to a complete loss of <italic>var</italic> transcriptional memory and a decrease in cytoadherence in CD36 adherent parasites. AP2-O-knocked-down parasites exhibited also significant reductions in transmission through <italic>Anopheles</italic> 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.</p>