PfHDAC1 is an essential regulator of P. falciparum asexual proliferation and host cell invasion genes with a dynamic genomic occupancy responsive to artemisinin stress

The goal of this study was to characterize the Plasmodium falciparum histone deacetylase, PfHDAC,1 for its genomic occupancy and regulation of gene expression across the parasite asexual development cycle. We identify that PfHDAC1 overexpression is associated with enhanced parasite proliferation/invasion over consecutive invasion cycles, and enhanced expression of host-cell invasion associated gene sets. Furthermore, increased cellular abundance of PfHDAC1 is correlated with enhanced resistance to antimalarial drug dihydroartemisinin. Treatment of parasites with the antimalarial additionally results in reorganization of genomic occupancy of PfHDAC1. Finally we identify that PfHDAC1 deacetylase activity and its possible post-translational phosphorylation by PfCKII-alpha is sensitive to dihydroartemisinin exposure. Overall, our study highlights the genomic landscape under PfHDAC1 regulation and presents compelling evidence regarding its regulation of genes implicated in the host-cell invasion as well as response to drug stress. This become especially relevant in the light of emerging artemisinin resistance around the world.