Sequestration of host metabolism by an intracellular pathogen

  1. Lena Gehre
  2. Olivier Gorgette
  3. Stéphanie Perrinet
  4. Marie-Christine Prevost
  5. Mathieu Ducatez
  6. Amanda M Giebel
  7. David E Nelson
  8. Steven G Ball
  9. Agathe Subtil  Is a corresponding author
  1. Institut Pasteur, France
  2. Université de Lille, France
  3. Indiana University Bloomington, United States
  4. Indiana University School of Medicine, United States

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.

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Author details

  1. Lena Gehre

    Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Olivier Gorgette

    Plate-forme de Microscopie Ultrastructurale, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Stéphanie Perrinet

    Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Marie-Christine Prevost

    Plate-forme de Microscopie Ultrastructurale, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Mathieu Ducatez

    Unité de Glycobiologie Structurale et Fonctionnelle, Université de Lille, Lille, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Amanda M Giebel

    Department of Biology, Indiana University Bloomington, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. David E Nelson

    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Steven G Ball

    Unité de Glycobiologie Structurale et Fonctionnelle, Université de Lille, Lille, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Agathe Subtil

    Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France
    For correspondence
    asubtil@pasteur.fr
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2016, Gehre et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lena Gehre
  2. Olivier Gorgette
  3. Stéphanie Perrinet
  4. Marie-Christine Prevost
  5. Mathieu Ducatez
  6. Amanda M Giebel
  7. David E Nelson
  8. Steven G Ball
  9. Agathe Subtil
(2016)
Sequestration of host metabolism by an intracellular pathogen
eLife 5:e12552.
https://doi.org/10.7554/eLife.12552

Share this article

https://doi.org/10.7554/eLife.12552

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