Characterization of the apicomplexan amino acid transporter (ApiAT) family in Toxoplasma gondii

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 common to 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, which is associated with acute infections. In particular, we demonstrate that one such ApiAT protein, which we term Tg ApiAT5-3, is an exchanger for aromatic and large neutral amino acids that functions in L-tyrosine scavenging and amino acid homeostasis, and is important for parasite virulence. We also provide evidence for the existence of alternative aromatic amino acid uptake pathways in the parasite, and 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.