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Sequestration of host metabolism by an intracellular pathogen.

Gehre L, Gorgette O, Perrinet S, Prevost MC, Ducatez M, Giebel AM, Nelson DE, Ball SG, Subtil A - Elife (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

Glc flux in C. trachomatis infected cells.Early during the infectious cycle (left) the inclusion contains mostly RBs. This developmental form does not accumulate glycogen and uses ATP rather than Glc6P (Omsland et al., 2012). SLC35D2, and possibly other transporters, are recruited to the inclusion membrane and UDP-Glc is translocated into the inclusion lumen. The activity of chlamydial glycogen metabolism enzymes, secreted by RBs into the inclusion lumen, leads to the onset of luminal glycogen synthesis between 16 and 20 hpi. In addition, host glycogen is imported into the inclusion lumen through invagination of the inclusion membrane. In culture cells de novo synthesis predominates over bulk glycogen import. Later on (right), RBs start converting into EBs, which rely on Glc6P as energy source. EBs obtain Glc6P via the degradation of luminal glycogen into Glc1P, subsequently converted to Glc6P by the phosphoglucomutase (MrsA) and imported by UhpC. During RB to EB conversion T3S is turned off, allowing for intrabacterial activity of the glycogen metabolism enzymes, and glycogen accumulation in the bacteria.DOI:http://dx.doi.org/10.7554/eLife.12552.022
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fig8: Glc flux in C. trachomatis infected cells.Early during the infectious cycle (left) the inclusion contains mostly RBs. This developmental form does not accumulate glycogen and uses ATP rather than Glc6P (Omsland et al., 2012). SLC35D2, and possibly other transporters, are recruited to the inclusion membrane and UDP-Glc is translocated into the inclusion lumen. The activity of chlamydial glycogen metabolism enzymes, secreted by RBs into the inclusion lumen, leads to the onset of luminal glycogen synthesis between 16 and 20 hpi. In addition, host glycogen is imported into the inclusion lumen through invagination of the inclusion membrane. In culture cells de novo synthesis predominates over bulk glycogen import. Later on (right), RBs start converting into EBs, which rely on Glc6P as energy source. EBs obtain Glc6P via the degradation of luminal glycogen into Glc1P, subsequently converted to Glc6P by the phosphoglucomutase (MrsA) and imported by UhpC. During RB to EB conversion T3S is turned off, allowing for intrabacterial activity of the glycogen metabolism enzymes, and glycogen accumulation in the bacteria.DOI:http://dx.doi.org/10.7554/eLife.12552.022

Mentions: This work shows that two independent processes contribute to glycogen accumulation in the C. trachomatis inclusion lumen: bulk uptake from the host cytoplasm and de novo synthesis (Figure 8). It is a unique example of a bacterium utilizing the compartmentalization of eukaryotic cells, to the extent that energy stores are radically shifted toward the bacterium and made inaccessible to the host.10.7554/eLife.12552.022Figure 8.Glc flux in C. trachomatis infected cells.


Sequestration of host metabolism by an intracellular pathogen.

Gehre L, Gorgette O, Perrinet S, Prevost MC, Ducatez M, Giebel AM, Nelson DE, Ball SG, Subtil A - Elife (2016)

Glc flux in C. trachomatis infected cells.Early during the infectious cycle (left) the inclusion contains mostly RBs. This developmental form does not accumulate glycogen and uses ATP rather than Glc6P (Omsland et al., 2012). SLC35D2, and possibly other transporters, are recruited to the inclusion membrane and UDP-Glc is translocated into the inclusion lumen. The activity of chlamydial glycogen metabolism enzymes, secreted by RBs into the inclusion lumen, leads to the onset of luminal glycogen synthesis between 16 and 20 hpi. In addition, host glycogen is imported into the inclusion lumen through invagination of the inclusion membrane. In culture cells de novo synthesis predominates over bulk glycogen import. Later on (right), RBs start converting into EBs, which rely on Glc6P as energy source. EBs obtain Glc6P via the degradation of luminal glycogen into Glc1P, subsequently converted to Glc6P by the phosphoglucomutase (MrsA) and imported by UhpC. During RB to EB conversion T3S is turned off, allowing for intrabacterial activity of the glycogen metabolism enzymes, and glycogen accumulation in the bacteria.DOI:http://dx.doi.org/10.7554/eLife.12552.022
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829429&req=5

fig8: Glc flux in C. trachomatis infected cells.Early during the infectious cycle (left) the inclusion contains mostly RBs. This developmental form does not accumulate glycogen and uses ATP rather than Glc6P (Omsland et al., 2012). SLC35D2, and possibly other transporters, are recruited to the inclusion membrane and UDP-Glc is translocated into the inclusion lumen. The activity of chlamydial glycogen metabolism enzymes, secreted by RBs into the inclusion lumen, leads to the onset of luminal glycogen synthesis between 16 and 20 hpi. In addition, host glycogen is imported into the inclusion lumen through invagination of the inclusion membrane. In culture cells de novo synthesis predominates over bulk glycogen import. Later on (right), RBs start converting into EBs, which rely on Glc6P as energy source. EBs obtain Glc6P via the degradation of luminal glycogen into Glc1P, subsequently converted to Glc6P by the phosphoglucomutase (MrsA) and imported by UhpC. During RB to EB conversion T3S is turned off, allowing for intrabacterial activity of the glycogen metabolism enzymes, and glycogen accumulation in the bacteria.DOI:http://dx.doi.org/10.7554/eLife.12552.022
Mentions: This work shows that two independent processes contribute to glycogen accumulation in the C. trachomatis inclusion lumen: bulk uptake from the host cytoplasm and de novo synthesis (Figure 8). It is a unique example of a bacterium utilizing the compartmentalization of eukaryotic cells, to the extent that energy stores are radically shifted toward the bacterium and made inaccessible to the host.10.7554/eLife.12552.022Figure 8.Glc flux in C. trachomatis infected cells.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus