Studying cellular survival strategies in resource-scarce environments is vital for revealing novel starvation responses across diverse life forms. Substantial advancements have been achieved in understanding purine metabolism in higher eukaryotes. Nevertheless, our understanding of these processes in protozoans is incomplete. This study presents a comprehensive analysis of Toxoplasma's purine dependency due to the absence of purine synthesis pathways 1,2.

We developed a model to study purine starvation in Toxoplasma, revealing significant transcriptional changes in response to purine scarcity. This includes the upregulation of histone modifiers during starvation and the downregulation of rhoptry transcripts, which are crucial for host cell invasion 3. Additionally, the study delineates the stage-specific roles of TgENTs, notably TgENT1 and TgENT2, in the parasite lifecycle. Notably, the deletion of TgENT1 led to a reduced number of tissue cysts in infected mice, underscoring its importance in chronic infection. Furthermore, this study investigated the essential nature of TgENT3, whose deletion results in complete growth defects.

The outcomes of this project are anticipated to significantly enhance our understanding of purine acquisition and metabolism in intracellular parasites, shedding light on alternative evolutionary pathways that lead to distinct purine-sensing and scavenging strategies. This has broader implications for understanding metabolic adaptations in other intracellular parasites.

Kloehn, J., Hammoudi, P.-M. & Soldati-Favre, D. Metabolite salvage and restriction during infection — a tug of war between Toxoplasma gondii and its host. Syst. Biol. Nanobiotechnology 68, 104–114 (2021). Olson, W. J. et al. Dual metabolomic profiling uncovers Toxoplasma manipulation of the host metabolome and the discovery of a novel parasite metabolic capability. PLOS Pathog. 16, e1008432 (2020). Dubremetz, J. F. Rhoptries are major players in Toxoplasma gondii invasion and host cell interaction. Cell. Microbiol. 9, 841–848 (2007).