Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites

Esther Rajendran,Stefan Bröer,Stephen J Fairweather,Ian A Cockburn,Kiaran Kirk,Giel G Van Dooren,Yeping Cai,Sanduni V Hapuarachchi,Catherine M Miller,Nicholas C Smith

doi:10.1038/ncomms14455

Abstract

Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family—the Novel Putative Transporters (NPTs)—play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites.

Highlights

Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane
We demonstrate that an Novel Putative Transporters (NPTs) protein from T. gondii, termed toxodb.org and www.plasmodb.org with accession codes TGME49_215490 (TgNPT1), functions as a highly selective arginine transporter, essential for parasite growth and virulence
We show that T. gondii has a second broader-specificity cationic amino acid uptake pathway that transports both arginine and lysine, but which is not sufficient to support parasite growth under physiological conditions

Summary

Introduction

Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. We demonstrate that an NPT protein from T. gondii, termed TgNPT1, functions as a highly selective arginine transporter, essential for parasite growth and virulence.

Results

Conclusion