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The Cryptosporidium parasite that lives in the gut is a nasty invader that hides in the cells that lining the stomach and harms the intestines.
Infections with Cryptosporidium can be very dangerous, especially for kids. Even minor infections may cause long-term malnutrition, which can restrict development and have other long-term effects.
Cryptosporidium gets into epithelial cells in the stomach and reproduces there, which makes people suffer from severe diarrhea. This is particularly harmful for kids who live in areas where it is common and for those whose immune systems are weak. There aren’t any effective treatments, even though it has a big influence on public health across the world.
This parasite has changed throughout time such that it may live in the human stomach by following the body’s natural pathways and taking over its host’s metabolism. But the researchers found a technique to map this maze of survival pathways and cut off Cryptosporidium’s most essential lifelines as part of research that was published today in Cell.
The scientists worked together for a year to develop and produce an experiment that may reveal Cryptosporidium’s survival network.
They used CRISPR editing technology to do a genome-scale evaluation experiment in which they disabled over 20,000 protein-coding genes in human intestinal cells one at a time. They placed Cryptosporidium into the cells to observe how each gene influenced the parasite’s ability to live.
The researchers found that a group of genes that make cholesterol had a big impact on the parasites’ ability to stay alive. But some of these genes seemed to stop Cryptosporidium from growing, while others boosted its growth.
This balance depended on a protein called squalene that was in the middle of the cholesterol production line. Getting rid of genes before they made squalene stopped infections, but getting rid of genes after they made squalene made infections worse.
A number of glands in our skin make squalene, which is known to protect the skin, especially against oxidative stress. The researchers found that squalene has a similar effect in the intestine: when squalene levels are high, reactive oxygen species (a marker of oxidative stress) are low.
Glutathione is the main chemical that people utilize to reduce reactive stress. This antioxidant is very important for preventing oxidation damage, and almost all living things can make it. The team was surprised to find that the Cryptosporidium parasite can use glutathione yet cannot make its own. The parasite then needs glutathione from the gut and is more likely to be harmed by oxidative stress.
Cryptosporidium lost the ability to make glutathione at some point in its evolution. Now, it uses the host’s production of this important molecule instead. This might be a smart way for Cryptosporidium to save energy for other tasks, but researchers have shown that it could also be dangerous for it.
Sources:
N. Bishara Marzook et al. (2025). The essential host genome for Cryptosporidium survival exposes metabolic dependencies that can be leveraged for treatment, Cell. DOI: 10.1016/j.cell.2025.07.001
Intestinal damage results from hidden cryptosporidium cell invasion, study shows. https://phys.org/news/2025-07-intestinal-results-hidden-cryptosporidium-cell.html
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