Sequestration of host metabolism by an intracellular pathogen

Lena Gehre (1) , Olivier Gorgette (2) , Stéphanie Perrinet (1) , Marie-Christine Prevost (2) , Mathieu Ducatez (3) , Amanda M Giebel (4) , David E Nelson (5) , Steven G Ball (3) , Agathe Subtil (1)

1 Biologie cellulaire de l'Infection microbienne - Cellular Biology of Microbial Infection
2 Microscopie électronique (Plate-forme)
3 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576
4 Indiana University [Bloomington]
5 Indiana University School of Medicine

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.

Keywords: cell biology; chlamydia trachomatis; glycogen metabolism; host-pathogen interactions; human; infectious disease; intracellular parasites; microbiology

Domains: Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Cellular Biology; Cell Behavior [q-bio.CB]; Life Sciences [q-bio]; Genetics; Human genetics; Life Sciences [q-bio]; Human health and pathology; Pulmonology and respiratory tract; Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology

Lena Gehre, Olivier Gorgette, Stéphanie Perrinet, Marie-Christine Prevost, Mathieu Ducatez, et al.. Sequestration of host metabolism by an intracellular pathogen. eLife, 2016, 5, pp.e12552. ⟨10.7554/eLife.12552⟩. ⟨pasteur-01397781⟩