Sequestration of host metabolism by an intracellular pathogen.

Autor: Gehre L; Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France.; CNRS UMR3691, Paris, France., Gorgette O; Plate-forme de Microscopie Ultrastructurale, Imagopole, Institut Pasteur, Paris, France., Perrinet S; Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France.; CNRS UMR3691, Paris, France., Prevost MC; Plate-forme de Microscopie Ultrastructurale, Imagopole, Institut Pasteur, Paris, France., Ducatez M; Unité de Glycobiologie Structurale et Fonctionnelle - CNRS UMR8576, Université de Lille, Lille, France., Giebel AM; Department of Biology, Indiana University Bloomington, Bloomington, United States., Nelson DE; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, United States., Ball SG; Unité de Glycobiologie Structurale et Fonctionnelle - CNRS UMR8576, Université de Lille, Lille, France., Subtil A; Unité de Biologie cellulaire de l'infection microbienne, Institut Pasteur, Paris, France.; CNRS UMR3691, Paris, France.
Jazyk: angličtina
Zdroj: ELife [Elife] 2016 Mar 16; Vol. 5, pp. e12552. Date of Electronic Publication: 2016 Mar 16.
DOI: 10.7554/eLife.12552
Abstrakt: 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.
Databáze: MEDLINE