Sequestration of host metabolism by an intracellular pathogen

• Main Authors: Lena Gehre, Olivier Gorgette, Stéphanie Perrinet, Marie-Christine Prevost, Mathieu Ducatez, Amanda M Giebel, David E Nelson, Steven G Ball, Agathe Subtil
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2016-03-01
• Series: eLife
• Subjects: chlamydia trachomatis; host-pathogen interactions; intracellular parasites; glycogen metabolism
• Online Access: https://elifesciences.org/articles/12552

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.