title: Phosphorylation of eukaryotic initiation factor-2{alpha} promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii.
abstract: While seeking a new host cell, obligate intracellular parasites, such as the protozoan Toxoplasma gondii, must be able to endure the stress of an extracellular environment. The mechanisms Toxoplasma use to remain viable while deprived of a host cell are not understood. We have previously shown that phosphorylation of Toxoplasma eukaryotic initiation factor-2α (TgIF2α) is a conserved response to stress. Here we report the characterization of Toxoplasma harboring a point mutation (S71A) in TgIF2α that prevents phosphorylation. Results show that TgIF2α phosphorylation is critical for parasite viability because the TgIF2α-S71A mutants are ill-equipped to cope with life outside the host cell. The TgIF2α-S71A mutants also showed a significant delay in producing acute toxoplasmosis in vivo. We conclude that the phosphorylation of TgIF2α plays a crucial role during the lytic cycle by ameliorating the stress of the extracellular environment while the parasite searches for a new host cell.
authors.affiliation: Departments of Pharmacology and Toxicology and Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Joyce
authors.forename: Sherry F
authors.initials: SF
authors.lastname: Queener
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Wek
authors.forename: William J
authors.initials: WJ
authors.lastname: Sullivan
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D030801:Animals, Genetically Modified; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006790:Host-Parasite Interactions / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010766:Phosphorylation; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology*; D014123:Toxoplasmosis / Q000378:metabolism / Q000469:parasitology
chemical_list: D015852:Eukaryotic Initiation Factor-2; D015800:Protozoan Proteins