title: Sequestration of host metabolism by an intracellular pathogen.
abstract: For intracellular pathogens, residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients. The human pathogen Chlamydia trachomatis grows in a glycogen-rich vacuole. How this large polymer accumulates there is unknown. We reveal that host glycogen stores shift to the vacuole through two pathways: bulk uptake from the cytoplasmic pool, and de novo synthesis. We provide evidence that bacterial glycogen metabolism enzymes are secreted into the vacuole lumen through type 3 secretion. Our data bring strong support to the following scenario: bacteria co-opt the host transporter SLC35D2 to import UDP-glucose into the vacuole, where it serves as substrate for de novo glycogen synthesis, through a remarkable adaptation of the bacterial glycogen synthase. Based on these findings we propose that parasitophorous vacuoles not only offer protection but also provide a microorganism-controlled metabolically active compartment essential for redirecting host resources to the pathogens.
authors.affiliation: Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France.|CNRS UMR3691, Paris, France.
authors.forename: Lena
authors.initials: L
authors.lastname: Gehre
authors.affiliation: Plate-forme de Microscopie Ultrastructurale, Imagopole, Institut Pasteur, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gorgette
authors.affiliation: Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France.|CNRS UMR3691, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Perrinet
authors.affiliation: Plate-forme de Microscopie Ultrastructurale, Imagopole, Institut Pasteur, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prevost
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle - CNRS UMR8576, Université de Lille, Lille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ducatez
authors.affiliation: Department of Biology, Indiana University Bloomington, Bloomington, United States.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Giebel
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Nelson
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle - CNRS UMR8576, Université de Lille, Lille, France.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Ball
authors.affiliation: Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France.|CNRS UMR3691, Paris, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Subtil
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D033704:Nucleotide Transport Proteins / Q000378:metabolism; D014532:Uridine Diphosphate Glucose / Q000378:metabolism; D014617:Vacuoles / Q000737:chemistry* / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D033704:Nucleotide Transport Proteins; C487823:SLC35D2 protein, human; D006003:Glycogen; D006006:Glycogen Synthase; D014532:Uridine Diphosphate Glucose
keywords: cell biology; chlamydia trachomatis; glycogen metabolism; host-pathogen interactions; human; infectious disease; intracellular parasites; microbiology