title: Toxoplasma gondii salvages sphingolipids from the host Golgi through the rerouting of selected Rab vesicles to the parasitophorous vacuole.
abstract: The obligate intracellular protozoan Toxoplasma gondii actively invades mammalian cells and, upon entry, forms its own membrane-bound compartment, named the parasitophorous vacuole (PV). Within the PV, the parasite replicates and scavenges nutrients, including lipids, from host organelles. Although T. gondii can synthesize sphingolipids de novo, it also scavenges these lipids from the host Golgi. How the parasite obtains sphingolipids from the Golgi remains unclear, as the PV avoids fusion with host organelles. In this study, we explore the host Golgi-PV interaction and evaluate the importance of host-derived sphingolipids for parasite growth. We demonstrate that the PV preferentially localizes near the host Golgi early during infection and remains closely associated with this organelle throughout infection. The parasite subverts the structure of the host Golgi, resulting in its fragmentation into numerous ministacks, which surround the PV, and hijacks host Golgi-derived vesicles within the PV. These vesicles, marked with Rab14, Rab30, or Rab43, colocalize with host-derived sphingolipids in the vacuolar space. Scavenged sphingolipids contribute to parasite replication since alterations in host sphingolipid metabolism are detrimental for the parasite's growth. Thus our results reveal that T. gondii relies on host-derived sphingolipids for its development and scavenges these lipids via Golgi-derived vesicles.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. jromano@jhsph.edu
authors.forename: Julia D
authors.initials: JD
authors.lastname: Romano
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sonda
authors.forename: Emily
authors.initials: E
authors.lastname: Bergbower
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Smith
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coppens
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000469:parasitology / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism* / Q000469:parasitology / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006790:Host-Parasite Interactions; D006801:Humans; D015151:Immunoblotting; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009154:Mutation; D013107:Sphingolipids / Q000378:metabolism*; D014122:Toxoplasma / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D014617:Vacuoles / Q000378:metabolism* / Q000469:parasitology / Q000648:ultrastructure; D014709:Vero Cells; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D049452:Green Fluorescent Proteins; D013107:Sphingolipids; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C101860:RAB30 protein, human; C553411:Rab14 protein, human