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

Autor: Cubillos EFG; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Prata IO; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Fotoran WL; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Ranford-Cartwright L; Institute of Biodiversity, Animal Health & Comparative Medicine, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, United Kingdom., Wunderlich G; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2021 Jun 28; Vol. 11, pp. 669088. Date of Electronic Publication: 2021 Jun 28 (Print Publication: 2021).
DOI: 10.3389/fcimb.2021.669088
Abstrakt: 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Cubillos, Prata, Fotoran, Ranford-Cartwright and Wunderlich.)
Databáze: MEDLINE