title: Phosphatidylthreonine and Lipid-Mediated Control of Parasite Virulence.
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.
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Ruben D
authors.initials: RD
authors.lastname: Arroyo-Olarte
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Biomembranes, Utrecht University, The Netherlands.
authors.forename: Jos F
authors.initials: JF
authors.lastname: Brouwers
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Arunakar
authors.initials: A
authors.lastname: Kuchipudi
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Biomembranes, Utrecht University, The Netherlands.
authors.forename: J Bernd
authors.initials: JB
authors.lastname: Helms
authors.affiliation: Institute of Medical Microbiology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Aindrila
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Institute of Medical Microbiology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Ildiko R
authors.initials: IR
authors.lastname: Dunay
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Lucius
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.|Parasitology Unit, Max-Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Nishith
authors.initials: N
authors.lastname: Gupta
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D030781:Organisms, Genetically Modified / Q000276:immunology / Q000378:metabolism; D000069289:Parasite Encystment; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016052:Protozoan Vaccines / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D013912:Threonine / Q000031:analogs & derivatives* / Q000378:metabolism; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D014123:Toxoplasmosis / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014613:Vaccines, Attenuated / Q000627:therapeutic use; D014774:Virulence
chemical_list: D020404:Glycerophospholipids; D010446:Peptide Fragments; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; C017629:phosphatidylthreonine; D013912:Threonine; D017855:Transferases (Other Substituted Phosphate Groups)