Date Published: February 11, 2019
Publisher: Public Library of Science
Author(s): Kathryn E. R. Parker, Stephen J. Fairweather, Esther Rajendran, Martin Blume, Malcolm J. McConville, Stefan Bröer, Kiaran Kirk, Giel G. van Dooren, Dominique Soldati-Favre.
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.
Apicomplexans are intracellular parasites that cause a range of diseases in humans and animals, imposing a major health and economic burden on many countries. In humans, Plasmodium species are the causative agents of malaria , while Cryptosporidium is a major cause of diarrheal disease and death in children in the developing world . Toxoplasma gondii can infect virtually all nucleated cells in warm-blooded animals, and is thought to chronically infect one-third of the world’s human population. 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 .
Parasites must scavenge essential amino acids from their environment, although, in the case of apicomplexan parasites, how they do so is poorly understood. We showed recently that uptake of cationic amino acids in T. gondii and P. berghei is mediated by members of a family of polytopic membrane transporters . Here, we have investigated the function of other members of this family and show that one of these proteins, TgApiAT5-3 functions is an aromatic amino acid transporter. Based in these findings, we have renamed this family of proteins Apicomplexan Amino acid Transporters (ApiATs).