The tyrosine transporter of Toxoplasma gondii is a member of the newly defined apicomplexan amino acid transporter (ApiAT) family.

Kathryn E R Parker,Malcolm J Mcconville,Kiaran Kirk,Giel G Van Dooren,Stefan Bröer,Esther Rajendran,Stephen J Fairweather,Martin Blume,Dominique Soldati-Favre

doi:10.1371/journal.ppat.1007577

Kathryn E R Parker, Malcolm J Mcconville + Show 7 more

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https://doi.org/10.1371/journal.ppat.1007577

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Abstract

Apicomplexan parasites are auxotrophic for a range of amino acids which must be salvaged from their host cells, either through direct uptake or degradation of host proteins. Here, we describe a family of plasma membrane-localized amino acid transporters, termed the Apicomplexan Amino acid Transporters (ApiATs), that are ubiquitous in apicomplexan parasites. Functional characterization of the ApiATs of Toxoplasma gondii indicate that several of these transporters are important for intracellular growth of the tachyzoite stage of the parasite, which is responsible for acute infections. We demonstrate that the ApiAT protein TgApiAT5-3 is an exchanger for aromatic and large neutral amino acids, with particular importance for L-tyrosine scavenging and amino acid homeostasis, and that TgApiAT5-3 is critical for parasite virulence. Our data indicate that T. gondii expresses additional proteins involved in the uptake of aromatic amino acids, and we present a model for the uptake and homeostasis of these amino acids. Our findings identify a family of amino acid transporters in apicomplexans, and highlight the importance of amino acid scavenging for the biology of this important phylum of intracellular parasites.

Highlights

Apicomplexans are intracellular parasites that cause a range of diseases in humans and animals, imposing a major health and economic burden on many countries
We conclude that NPTs are a family of amino acid transporter proteins found in apicomplexans, and we propose that the family be renamed the Apicomplexan Amino acid Transporter (ApiAT) family
To identify ApiAT-family proteins in the apicomplexan parasites T. gondii, Neospora caninum, Eimeria tenella, P. falciparum, P. berghei, Theileria annulata, Babesia bovis and Cryptosporidium parvum, we undertook Basic Local Alignment Search Tool (BLAST) searches using each of the five P. falciparum ApiATs as initial query sequences We undertook BLAST searches of the genomes from the chromerids Chromera velia and Vitrella brassicaformis, which are close free-living relatives of apicomplexans [15]

Summary

Introduction

Apicomplexans are intracellular parasites that cause a range of diseases in humans and animals, imposing a major health and economic burden on many countries. Plasmodium species are the causative agents of malaria [1], while Cryptosporidium is a major cause of diarrheal disease and death in children in the developing world [2]. T. gondii infections are usually asymptomatic, but infection in immunocompromised patients may lead to life-threatening toxoplasmic encephalitis, and congenital toxoplasmosis may result in severe birth defects or death of the developing fetus [3]. Transporters provide the major route for the acquisition of nutrients and the removal of waste products across the plasma membrane [5, 7], and these proteins are important for parasite survival and virulence [8, 9]. The transporters responsible for the uptake of many essential nutrients in apicomplexans have not been defined

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