AsianScientist (Aug. 21 2015) – The extraordinary capacity of Toxoplasma gondii to infect different cells is due to its very broad culinary states for different types of sugars, according to a study by researchers from the University of Melbourne. Their findings, published in Cell Host and Microbe, could lead to new drug targets for Toxoplasmosis, a condition caused by Toxoplasma infection.
Toxoplasmosis is estimated to chronically infect nearly one-third of the world’s population. It is most commonly associated with handling cat feces and is a threat to pregnant women and immune-compromised individuals in particular. It may also be implicated in mental illnesses, such as schizophrenia and depression. Toxoplasma has an unusual ability to infect any warm-blooded animal cell, ranging from immune cells to brain cells.
Scavenging nutrients such as glucose from the host cell is one of the biggest challenges that microbial pathogens face. First author Martin Blume and colleagues demonstrated that Toxoplasma is able to steal and utilize a range of energy-rich nutrients from the host cell, allowing it to adapt to different host cell niches.
Professor Malcolm McConville, the corresponding author, said that unlike other pathogens that tend to only use one nutrient at a time, Toxoplasma, can use multiple nutrients at the same time.
“This may give these parasites enormous flexibility as well as the ability to grow in a range of different host cell types,” McConville said.
“Being adaptable is good, but it comes at the cost of having to make all of the enzymes needed to metabolize these nutrients all the time. This is an apparently wasteful exercise.”
However, the researchers have shown that Toxoplasma repurposes some of these enzymes, so that they improve nutrient metabolism, regardless of the nutrient being used. Toxoplasma has managed to tweak its metabolism in a way that allows it to be both adaptable and efficient, allowing it to colonize a new animal or human host and grow very rapidly.
But its survival advantage may also turn out to be its Achilles’ heel.
At least one of the enzymes that is switched on all of the time, TgFBP2, is also needed when parasites are using nutrients that are not normally metabolised by the enzyme. When the function of TgFBP2 is blocked, Toxoplasma is no longer infectious.
This new insight makes it possible to develop drugs that specifically target and block TgFBP2 to prevent acute Toxoplasma infection.
The article can be found at: Blume et al. (2015) A Toxoplasma gondii Gluconeogenic Enzyme Contributes to Robust Central Carbon Metabolism and Is Essential for Replication and Virulence.
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Source: The University of Melbourne; Photo: Yale Rosen/Flickr/CC.
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