Metabolic interactions between Toxoplasma gondii and its host

Abstract

Toxoplasma gondii is an obligate intracellular parasite belonging to the phylum Apicomplexa that infects all warm-blooded animals, including humans. T. gondii can replicate in every nucleated host cell by orchestrating metabolic interactions to derive crucial nutrients. In this review, we summarize the current status of known metabolic interactions of T. gondii with its host cell and discuss open questions and promising experimental approaches that will allow further dissection of the host-parasite interface and discovery of ways to efficiently target both tachyzoite and bradyzoite forms of T. gondii, which are associated with acute and chronic infection, respectively.

Keywords: Metabolism; bradyzoite; intracellular parasite; metabolomics.

Figure 1.. Quantitative comparison of computationally annotated transporters between parasitic and non-parasitic unicellular organisms.

Data were extracted from TransportDB 2.0 . Dark-colored bars represent the numbers of different transporter families per given genome, whereas the light-colored bars give the percentage of all predicted transporter proteins per entirety of open reading frames (ORFs). Green indicates parasitic organisms and black indicates free-living organisms. *Data are from since Toxoplasma gondii is absent in the current release of TransportDB 2.0. The inlet provides the mean ± standard deviation of the number of families of both groups. For comparison, intracellular bacteria (red) and humans (blue) are also shown.

Figure 2.. Currently known or predicted dependencies of Toxoplasma gondii tachyzoites on host cell–derived metabolites.

Based on data from , . Two T. gondii tachyzoites within a parasitophorous vacuole (light blue) are shown within a fibroblast host cell (gray). Red arrowheads indicate uptake of compounds that can be synthesized by mammalian cells, whereas brown arrowheads mark uptake of those substances for which both organisms are auxotrophic and thus they compete. Metabolites in black are scavenged when available but are not strictly essential whereas the pathways they are involved in are. Blue arrowheads denote the end products for which the imported metabolites are precursors or essential co-factors (or both) for their synthesis. Lipoic acid (pink) is special since it is synthesized in one compartment of the parasite (apicoplast) but apparently unable to reach another organelle (mitochondrion) where it is also required; thus, it has to be scavenged from the host . ¹L-Arg; L-Trp; L-His; L-Lys (or L-2-aminoadipate 6-semialdehyde); L-Ile (or (S)-3-methyl-2-oxopentanoate); L-Val (or 3-methyl-2-oxobutanoate); L-Leu (or 4-methyl-2-oxo-pentanoate); L-Phe (or phenylpyruvate). ²Nicotinate or nicotinate-D-ribonucleoside or nicotinamide. ³Putrescine, spermine, ornithine. ⁴D-fructose or D-glucosamine or D-glucose or D-mannose or D-ribose or D-sorbitol or 2-Deoxy-D-ribose. ⁵Adenine or adenosine or guanine or guanosine or inosine or hypoxanthine or xanthine. ⁶Phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid. ⁷Uracil, uridine, cytidine, deoxyuridine, deoxycytidine.