Phosphatidylthreonine and Lipid-Mediated Control of Parasite Virulence |
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| Authors: | Ruben D Arroyo-Olarte Jos F Brouwers Arunakar Kuchipudi J Bernd Helms Aindrila Biswas Ildiko R Dunay Richard Lucius Nishith Gupta |
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| Institution: | 1Department of Molecular Parasitology, Humboldt University, Berlin, Germany;2Department of Biochemistry and Cell Biology, Institute of Biomembranes, Utrecht University, The Netherlands;3Institute of Medical Microbiology, Otto von Guericke University, Magdeburg, Germany;4Parasitology Unit, Max-Planck Institute for Infection Biology, Berlin, Germany;University of Vermont, UNITED STATES |
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| Abstract: | The major membrane phospholipid classes, described thus far, include phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylserine (PtdSer), and phosphatidylinositol (PtdIns). Here, we demonstrate the natural occurrence and genetic origin of an exclusive and rather abundant lipid, phosphatidylthreonine (PtdThr), in a common eukaryotic model parasite, Toxoplasma gondii. The parasite expresses a novel enzyme PtdThr synthase (TgPTS) to produce this lipid in its endoplasmic reticulum. Genetic disruption of TgPTS abrogates de novo synthesis of PtdThr and impairs the lytic cycle and virulence of T. gondii. The observed phenotype is caused by a reduced gliding motility, which blights the parasite egress and ensuing host cell invasion. Notably, the PTS mutant can prevent acute as well as yet-incurable chronic toxoplasmosis in a mouse model, which endorses its potential clinical utility as a metabolically attenuated vaccine. Together, the work also illustrates the functional speciation of two evolutionarily related membrane phospholipids, i.e., PtdThr and PtdSer. |
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