Defining the Apicomplexan Amino Acid Transporter (ApiAT) Family

The Apicomplexan phylum is a large group of unicellular eukaryotic parasites. These parasites cause some notorious diseases of humankind, including malaria and toxoplasmosis. Apicomplexan parasites can also infect animal species, causing significant animal suffering and economic loss in the livestock industry. The advent of drug resistance and the poor side-effect profiles of some medications provides impetus for the development of new anti-parasitic drugs. Uncovering key aspects of parasite biology may aid in identifying and characterising novel inhibitors of parasite growth. Disruption of nutrient acquisition is one avenue to halt parasite replication and thereby cure infections. Parasites, by definition, rely on their hosts for a source of nutrients. Most nutrients do not diffuse freely across cellular membranes and their acquisition relies on cell-derived processes. One means by which parasites can acquire nutrients is via transporter proteins. Transporters are integral membrane proteins that mediate the movement of solutes across biological membranes. Apart from nutrient acquisition, transporters are also a means by which cells remove waste products and toxins, and control their ionic composition. Despite their importance, the transporters that allow apicomplexan parasites to perform these cell functions are currently not well characterised. Here, I define a family of amino acid transporters that are ubiquitous in apicomplexan parasites, which I name Apicomplexan Amino acid Transporters (ApiATs). I show that 10 of the 16 ApiATs in Toxoplasma gondii are expressed in the disease-causing tachyzoite stage, and 8 of them localise to the parasite plasma membrane. I demonstrate that four ApiAT proteins are important for growth of the tachyzoite stage of the parasite. In T. gondii, the amino acid glutamine is of particular interest because, apart from its role in protein synthesis, it is also used as an energy source. Prior to this work the uptake mechanism for glutamine in T. gondii was unknown. I investigated the substrate specificities of one ApiAT protein, TgApiAT2, demonstrating that it functions as a neutral amino acid transporter and is the major glutamine transporter of the parasite. Together, these 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