Gehre, LenaGorgette, OlivierPerrinet, StéphaniePrevost, Marie-ChristineDucatez, MathieuGiebel, Amanda M.Nelson, David E.Ball, Steven G.Subtil, Agathe2016-09-072016-09-072016Gehre, L., Gorgette, O., Perrinet, S., Prevost, M.-C., Ducatez, M., Giebel, A. M., … Subtil, A. (2016). Sequestration of host metabolism by an intracellular pathogen. eLife, 5, e12552. http://doi.org/10.7554/eLife.125522050-084Xhttps://hdl.handle.net/1805/10872For 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.en-USAttribution 3.0 United Statescell biologychlamydia trachomatisglycogen metabolismhost-pathogen interactionsHumansinfectious diseaseintracellular parasitesmicrobiologyArticle