Metabolic regulation of sexual commitment in Plasmodium falciparum

Abstract

For malaria parasites regulating sexual commitment, the frequency with which asexual bloodstream forms differentiate into non-replicative male and female gametocytes, is critical because asexual replication is required to maintain a persistent infection of the human host while gametocytes are essential for infection of the mosquito vector and transmission. Here, we describe recent advances in understanding of the regulatory mechanisms controlling this key developmental decision. These include new insights into the mechanistic roles of the transcriptional master switch AP2-G and the epigenetic modulator GDV1, as well as the identification of defined metabolic signals that modulate their activity. Many of these metabolites are linked to parasite phospholipid biogenesis and we propose a model linking this pathway to the epigenetic regulation underlying sexual commitment in P. falciparum.

Figure 1:

Metabolic model connecting the availability of phosphatidylcholine precursors to heterochromatin maintenance via the shared methylation donor and inhibitors SAM and SAH used in both histone methylation and de novo phospho-choline synthesis. Factors known or expected to increase the frequency of sexual commitment are in orange and those known or expected to repress sexual commitment are shown in blue.