# PfApiAT2 is a proline transporter essential for the transmission of Plasmodium falciparum by the mosquito vector

## TL;DR

This study identifies a proline transporter in malaria parasites that is crucial for their development in mosquitoes, revealing a new target to block malaria transmission.

## Contribution

The study reveals PfApiAT2 as a proline transporter essential for Plasmodium falciparum oocyst development in mosquitoes.

## Key findings

- PfApiAT2 is a proline-specific transporter required for early oocyst development in Anopheles gambiae.
- Halofuginone-resistant and PfApiAT2-knockout parasites form defective oocysts with impaired sporozoite production.
- Mosquito nutrient supplementation rescues the growth defect of PfApiAT2-deficient parasites.

## Abstract

Plasmodium falciparum oocysts undergo an explosive biomass increase during development in Anopheles mosquitoes, a dramatic growth process likely promoted by as-yet unknown nutrients scavenged from the mosquito. We previously observed in blood-stage parasites, that the amino acid transporter PfApiAT2, although dispensable, regulates proline homeostasis and mediates resistance to halofuginone, a potent proline-tRNA synthetase inhibitor. Here, we demonstrate that PfApiAT2 is a proline-specific transporter essential for early oocyst development in Anopheles gambiae. Halofuginone-resistant pfapiat2-mutant parasites form stunted oocysts severely defective in sporozoite production. This phenotype is recapitulated in PfApiAT2-knockout parasites that undergo a complete block in sporogony, forming oocysts that stall and degenerate. Remarkably, this growth defect can be rescued by nutrient supplementation to the mosquito vector. By identifying an amino acid transporter essential for oocyst growth, our data unveil a vulnerability in P. falciparum transmission, revealing a critical nutritional dependency of the parasite on its mosquito vector.