The exponential asexual replication of P. falciparum in red blood cells results in either asymptomatic, uncomplicated or complicated malaria. However, approximately 1% of infected erythrocytes differentiate into non-replicative sexual forms (gametocytes), which are essential players in malaria transmission since they are taken up by the mosquito vector for further maturation. The proportion of parasites that converts into their sexual forms at each replicative cycle, also known as the sexual conversion rate, is tightly regulated. Increasing evidence suggests that parasites respond to certain environmental factors by adjusting their sexual conversion rate, which reflects the trade-off between parasite transmission and within-host survival. Recently, epigenetic activation of the transcription factor PfAP2-G was discovered as a master regulator event in the sexual commitment process that leads to parasite conversion into gametocytes. Moreover, conditions that increase gametocyte production have been linked to increased stress towards the parasite, including overgrowing blood stage cultures, cultures with parasite-spent medium and cultures depleted of lysophosphatidylcholine. This indicates an important influence of the host metabolism on sexual conversion. Dysmetabolism is also closely linked with inflammation, and both are tightly associated with malarial complications, but their effect on the sexual conversion of the parasite is unknown.
|Effective start/end date||20/10/20 → 31/12/21|
- Flemish Government - Department of Economy, Science & Innovation: €24,563.00