Ceramide biosynthesis is critical for establishment of the intracellular niche of Toxoplasma gondii
SUMMARY
Toxoplasma gondii possesses sphingolipid synthesis capabilities and is equipped to salvage lipids from its host. The contribution of these two routes of lipid acquisition during parasite development is unclear. As part of a complete ceramide synthesis pathway, T. gondii expresses two serine palmitoyltransferases (TgSPT1 and TgSPT2) and a dihydroceramide desaturase. The research group of GCIR member Professor Dominique Soldati-Favre determines in this article published in Cell Reports the role of these genes in parasite development in vitro and in vivo during acute and chronic infection. Detailed phenotyping through lipidomic approaches reveal a perturbed sphingolipidome in these mutants, characterized by a drastic reduction in ceramides and ceramide phosphoethanolamines but not sphingomyelins. Critically, parasites lacking TgSPT1 display decreased fitness, marked by reduced growth rates and a selective defect in rhoptry discharge in the form of secretory vesicles, causing an invasion defect. Disruption of de novo ceramide synthesis modestly affects acute infection in vivo but severely reduces cyst burden in the brain of chronically infected mice.
This research was supported by the Swiss National Foundation Sinergia and the European Research Council (ERC) under European Union Horizon 2020 research and innovation program.
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Why is this article important?
Toxoplasma gondii is the most ubiquitous member of the Apicomplexa phylum, infecting all warm-blooded animals and prevalent in one third of the global human population (Montoya and Liesenfeld, 2004). Although infection is commonly asymptomatic, it can cause severe disease in immunocompromised individuals, including individuals with HIV and chemotherapy and organ transplant recipients, or result in miscarriage or congenital anomalies when primary infection occurs during pregnancy.
T. gondii is an obligate intravacuolar pathogen that has evolved strategies to exploit host cell lipid metabolism (Shunmugam et al., 2022). Lipid metabolism and acquisition are central to the parasitic lifestyle. This study unravels the remarkable plasticity of T. gondii for lipid acquisition, ranging from de novo synthesis to salvage of sphingolipids, including uptake and processing of salvaged intermediates. This plasticity likely contributes to the adaptability of T. gondii to a broad host cell spectrum that is unmatched by other apicomplexans.
22 Aug 2022