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

Author(s)

Cubillos, Eliana F. G. ^[1] ; Prata, Isadora Oliveira ^[1] ; Fotoran, Wesley Luzetti ^[1] ; Ranford-Cartwright, Lisa ^[2] ; Wunderlich, Gerhard ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] Univ Glasgow, Coll Med Vet & Life Sci, Inst Biodivers Anim Hlth & Comparat Med, Glasgow, Lanark - Scotland

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 11, JUN 28 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 16/12659-5 - Approaching the role of three ApiAP2 transcription factors in the control of gene transcription in intraerythrocytic and sexual stages of Plasmodium falciparum
• Grantee: Eliana Fernanda Galindo Cubillos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/24267-7 - Role of chromatin modifiers in the transcription dynamics of virulence factors of the human malaria parasite Plasmodium falciparum
• Grantee: Gerhard Wunderlich
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/17174-7 - Factors influencing expression of variant antigen families var, rif and surf of Plasmodium falciparum, the human malaria parasite
• Grantee: Gerhard Wunderlich
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/19145-7 - Application of liposomes for RNA vaccines against the Plasmodium falciparum PfHR5 antigen and establishment of a technical approach for guided liposomes
• Grantee: Wesley Luzetti Fotoran
• Support Opportunities: Scholarships in Brazil - Post-Doctoral