# Defining the Proteome of Sexually Committed Parasites in Plasmodium falciparum

## TL;DR

This study identifies a marker for sexually committed malaria parasites and uses it to analyze their proteome, revealing distinct protein signatures.

## Contribution

The first proteomic characterization of sexually committed Plasmodium falciparum parasites using a novel transgenic marker.

## Key findings

- MSRP1 is a specific marker for sexual commitment in P. falciparum.
- Proteomic analysis revealed distinct protein signatures in sexually committed parasites.
- MSP11 showed differential localization, validating its role in sexual commitment.

## Abstract

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.

•Generation of transgenic malaria parasites for FACS of sexually committed schizonts.•First proteomic characterization of sexually committed schizonts.•Differential localization validates candidate hit MSP11.•Blueprint for systematic characterization of sexually committed schizonts.

Generation of transgenic malaria parasites for FACS of sexually committed schizonts.

First proteomic characterization of sexually committed schizonts.

Differential localization validates candidate hit MSP11.

Blueprint for systematic characterization of sexually committed schizonts.

Malaria transmission from humans to mosquitoes is essential to the parasite life cycle yet major knowledge gaps remain. In particular the switch from asexual replication within red blood cells to formation of sexual transmission stages, i.e. sexual commitment, remains poorly understood. Here we use a transgenic reporter parasite line to isolate sexually committed cells by fluorescence-activated cell sorting for the first mass spectrometry analysis of this elusive parasite stage.