Defining the Proteome of Sexually Committed Parasites in Plasmodium falciparum

Malaria transmission from humans to mosquitoes is essential to the parasite life cycle. In the human malaria parasite, Plasmodium falciparum, the rate of commitment to produce the sexual transmission stages, or gametocytes varies and is governed by genetic, epigenetic and environmental factors. The sexually committed parasite has so far remained elusive due to the lack of markers to efficiently isolate these parasites for subsequent functional studies including proteomic analysis of the isolated population. Here, we demonstrate that MSRP1 is a highly specific sexual commitment marker. Using this marker, we generated and validated reporter parasite lines for subsequent FACS-based isolation of sexually and asexually committed parasites. Proteomics of isolated parasites defined distinct protein signatures, including several merozoite surface proteins, indicating functional differences between the two parasite populations. This study provides a blueprint for systematic characterization of the parasite stage at this crucial juncture in the life cycle.