Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor

Publication date: 14 June 2017
Source:Cell Host & Microbe, Volume 21, Issue 6
Author(s): Joana Mendonca Santos, Gabrielle Josling, Philipp Ross, Preeti Joshi, Lindsey Orchard, Tracey Campbell, Ariel Schieler, Ileana M. Cristea, Manuel Llinás
Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor PfAP2-I, belonging to the Apicomplexan AP2 (ApiAP2) family, that is responsible for regulating the expression of genes involved in RBC invasion. Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of target genes. Although PfAP2-I contains three AP2 DNA-binding domains, only one is required for binding of the target genes during blood stage development. Furthermore, we find that PfAP2-I associates with several chromatin-associated proteins, including the Plasmodium bromodomain protein PfBDP1 and that complex formation is associated with transcriptional regulation. As a key regulator of red blood cell invasion, PfAP2-I represents a potential new antimalarial therapeutic target.

Graphical abstract

Teaser

Invasion of red blood cells is a highly regulated and essential process in the life cycle of the malaria parasite Plasmodium falciparum. Santos et al. identify a transcription factor (PfAP2-I) that regulates invasion genes during blood stage development and associates with P. falciparum bromodomain protein 1 (PfBDP1).


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