Substrate-mediated regulation of the arginine transporter ofToxoplasma gondii

ABSTRACT Intracellular parasites, such as the apicomplexan Toxoplasma gondii , are adept at scavenging nutrients from their host. However, there is little understanding of how parasites sense and respond to the changing nutrient environments they encounter during an infection. Tg ApiAT1, a member of the apicomplexan ApiAT family of amino acid transporters, is the major uptake route for the essential amino acid L-arginine (Arg) in T. gondii . Here, we show that the abundance of Tg ApiAT1, and hence the rate of uptake of Arg, is regulated by the availability of Arg in the parasite’s external environment, increasing in response to decreased [Arg]. Using a luciferase-based ‘biosensor’ strain of T. gondii , we demonstrate that parasites vary the expression of Tg ApiAT1 in different organs within their host, indicating that parasites are able to modulate Tg ApiAT1-dependent uptake of Arg as they encounter different nutrient environments in vivo . Finally, we show that Arg-dependent regulation of Tg ApiAT1 expression is post-transcriptional, mediated by an upstream open reading frame (uORF) in the Tg ApiAT1 transcript, and we provide evidence that the peptide encoded by this uORF is critical for mediating regulation. Together, our data reveal the mechanism by which an apicomplexan parasite responds to changes in the availability of a key nutrient.