Part 6: Kiss and spit metabolomics highlight the role of host purine metabolism during pathogen infection

Intracellular bacteria and protists rely on the host cell to supply many
metabolites, but the mechanisms through which pathogens manipulate host
metabolism to their benefit are not understood. Here, we demonstrate that
when the obligate intracellular parasite Toxoplasma gondii secretes its
rhoptry organelle contents into the host cytoplasm before invasion—a
process called “kiss and spit”—host cell metabolite abundance is altered
in nucleotide synthesis, the pentose phosphate pathway, glycolysis, and
amino acid synthesis. U-13C6 labeling metabolomics confirmed that kiss and
spit increased the flow of carbon through the pentose phosphate pathway
and nucleotide synthesis. An increase in 2,3-bisphosphoglycerate abundance
led us to investigate the activation of host cytosolic nucleosidase II
(cN-II) to provide purines for the parasite. We found that T.
gondii manipulates the host cN-II enzyme to dephosphorylate GMP and IMP
that it needs for replication. Further, we found that the approved
anti-cancer drug fludarabine, which inhibits cN-II, also
inhibits Toxoplasma replication. These results
reveal Toxoplasma host cell manipulation and highlight
potential therapies for toxoplasmosis. There are several datasets related
to T. gondii kiss and spit Part 1: Kiss and spit metabolomics
highlight the role of host purine metabolism during pathogen infection:
10.5061/dryad.b2rbnzsjd : Time course of T. gondii kiss and spit-HFF cells
metabolomics Part 2: Kiss and spit metabolomics highlight the
role of host purine metabolism during pathogen infection:
10.5061/dryad.69p8cz9b5:  U-13C6 labeling of ME49 T.
gondii  kiss and spit and full infection in HFF cells Part
3: Kiss and spit metabolomics highlight the role of host purine
metabolism during pathogen infection: 10.5061/dryad.9p8cz8wrn:
 Effect of fludarabine on purine metabolism in T.
gondii infected HFF host cells Part 4: Kiss and spit
metabolomics highlight the role of host purine metabolism during pathogen
infection: 10.5061/dryad.7d7wm383s: ME49T. gondii infected
MDAMB231 cells Metabolomics at 24 and 48 HPI Part 5: Kiss and
spit metabolomics highlight the role of host purine metabolism during
pathogen infection: 10.5061/dryad.ghx3ffbxx: Effect of AMP addition on
purine metabolism in T. gondii infected host cells at 48
HPI Part 6: Kiss and spit metabolomics highlight the role of host
purine metabolism during pathogen infection: 10.5061/dryad.zkh1893jn: ME49
T. gondii Kiss and spit negative controls