The regulation of the regulator of the regulator of the regulator of sexual conversion in Plasmodium falciparum [Nodes Seminar]

The protozoan parasite Plasmodium falciparum produces the majority of malaria cases and deaths. At each round of asexual replication in the human blood, some parasites convert into sexual precursors, called gametocytes, that are essential for human-to-vector transmission. The sexual conversion rate determines the relative parasite investment between infection in the same host and transmission. Sexual conversion is orchestrated by the master regulator PfAP2-G, a transcription factor of the ApiAP2 family. However, how the expression of PfAP2-G is regulated and activated in response to specific conditions of the blood environment remains poorly understood. I will present new insight into the complex regulatory mechanism of sexual conversion, which involves another transcription factor, a chromatin modifier, a non-coding antisense RNA, epigenetic changes in heterochromatin at a specific locus, and positive and negative feedback loops.