Sequestration of host metabolism by an intracellular pathogen

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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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Lena Gehre

Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France

Competing interests
The authors declare that no competing interests exist.
Olivier Gorgette

Plate-forme de Microscopie Ultrastructurale, Institut Pasteur, Paris, France

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The authors declare that no competing interests exist.
Stéphanie Perrinet

Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France

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The authors declare that no competing interests exist.
Marie-Christine Prevost

Plate-forme de Microscopie Ultrastructurale, Institut Pasteur, Paris, France

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The authors declare that no competing interests exist.
Mathieu Ducatez

Unité de Glycobiologie Structurale et Fonctionnelle, Université de Lille, Lille, France

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The authors declare that no competing interests exist.
Amanda M Giebel

Department of Biology, Indiana University Bloomington, Bloomington, United States

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The authors declare that no competing interests exist.
David E Nelson

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, United States

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The authors declare that no competing interests exist.
Steven G Ball

Unité de Glycobiologie Structurale et Fonctionnelle, Université de Lille, Lille, France

Competing interests
The authors declare that no competing interests exist.
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.

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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.