In the developed world, we often think of parasitic infections as diseases that only infect impoverished nations or adventurous travelers who trek to rural outreaches of the globe. However, the medically relevant parasite Toxoplasma gondii has been estimated to infect one-third of the world’s population and is the most common parasite in developed nations.
Typically, infected individuals remain asymptomatic throughout their lives never knowing they had the single-celled parasite roaming freely about their tissues. T. gondii is primarily a concern for pregnant women and immune-compromised individuals, such as those suffering from HIV/AIDS.
Interestingly, previous studies on mice have implicated T. gondii affecting behavior, as the parasite often invades neurons of the brain and has the capacity to infect almost any nucleated cell. Moreover, additional studies have connected the parasitic infection with mental illness such as schizophrenia and depression.
Now, researchers from the University of Melbourne have shown that the capacity of Toxoplasma to invade and take up residence in such a broad range of cell types is due to the parasite’s indiscriminate culinary pallet. Cellular subsistence is a fine balance between energy coming in and energy utilized to maintain metabolic functions. Small perturbations of this balance can have large impacts on an organism—especially parasites like T. gondii, who seemingly expend lots of energy in order to be so adaptable.
In the current study, the investigators observed that Toxoplasma was able to steal and utilize a range of energy-rich nutrients from the host cell, allowing it to adapt to different host cell niches.
“This may give these parasites enormous flexibility as well as the ability to grow in a range of different host cell types,” explained senior author Malcolm McConville, Ph.D., director at the Bio21 Institute in the Department of Biochemistry and Molecular Biology within the University of Melbourne. “Being adaptable is good, but it comes at the cost of having to make all of the enzymes need to metabolize these nutrients all of the time, an apparently wasteful exercise.”
The findings from this study were published recently in Cell Host and Microbe through an article entitled “A Toxoplasma gondii Gluconeogenic Enzyme Contributes to Robust Central Carbon Metabolism and Is Essential for Replication and Virulence.”
Dr. McConville and his team found that T. gondii was able to repurpose some metabolic enzymes so that they improve nutrient absorption, regardless of the nutrient being used. Moreover, at least one of the enzymes, which seem to be switched on all of the time, TgFBP2, is also needed when parasites are using nutrients that are not normally metabolized by the enzyme.
The scientists were able to show “that conditional knockdown of TgFBP2 results in complete loss of intracellular growth in vitro under glucose-replete conditions and loss of acute virulence in mice. TgFBP2 deficiency was rescued by expression of catalytically active FBPase and was associated with altered glycolytic and mitochondrial TCA cycle fluxes, as well as dysregulation of glycolipid, amylopectin, and fatty acid biosynthesis.”
These results open the possibility of developing drugs that specifically target TgFB2 and possibly prevent acute Toxoplasma infections. Additionally, this research may also be useful in the study of another disease-causing parasite in the same family as T. gondii—the causative agent of malaria, the Plasmodium parasite species.