Kiss and spit metabolomics highlights the role of host purine metabolism during pathogen infection

Abstract Intracellular bacteria and protists are auxotrophic for many metabolites and must rely on the host cell to supply these nutrients. The mechanisms of how pathogens manipulate host metabolism to their benefit are not understood. These questions are difficult to address for intracellular pathogens because one cannot easily distinguish the origin of the metabolite as host or pathogen derived. The obligate intracellular parasite Toxoplasma gondii manipulates the host cell by a pre-invasion process called “kiss and spit”, where the contents of the parasite rhoptry organelles are secreted into the host cytoplasm before invasion occurs. Here, we demonstrated that rhoptry contents from kiss and spit altered metabolite abundance in nucleotide synthesis, the pentose phosphate pathway, glycolysis, and amino acid synthesis. An increase in 2,3-bisphosphoglycerate (2,3-BPG) abundance led us to investigate the activation of host cytosolic nucleosidase II (cN-II) to provide purines for the parasite.