How the Cryptosporidium Parasite Alters Host Cells

Researchers at the Francis Crick Institute have shown that the Cryptosporidium parasite exports a protein into infected intestinal cells, altering the gut environment and enabling the parasite to survive and replicate.

Cryptosporidium is an intestinal parasite and one of the leading causes of severe diarrhoea in children. It invades and replicates inside epithelial cells that line the host intestine and is known to cause nutrient-absorbing projections called microvilli to grow.

In research published in Cell Host and Microbe, the lab at the Crick identified a family of proteins that Cryptosporidium injects into intestinal epithelial cells during an infection, which accumulate within the host microvilli.

The team investigated a major protein in this family, called microvilli protein 1 (MVP1), finding that, within the epithelial cell, it interacts with human proteins that are responsible for maintaining structure and regulating cellular projections like microvilli.

When MVP1 was removed from a strain of Cryptosporidium, using CRISPR-based genetic editing, the elongation of microvilli within infected cells was completely blocked. This strain of MVP1-deficient parasites also failed to cause a normal infection in mice.

One of the proteins that MVP1 interacts with, called EBP50, is crucial for stabilising pumps on the surface of the cells that bring salts in. Disrupting these pumps results in diarrhoea, so the team believes that MVP1 might be one of the key factors that drive the symptoms caused by Cryptosporidium. 

Adam Sateriale, Group Leader of the Cryptosporidiosis Laboratory at the Crick, said: “The disease caused by Cryptosporidium is particularly dangerous for children and it can lead to lasting malnutrition, but we still don’t understand how it causes symptoms. We’ve now begun to unravel how the parasite manipulates the structure of the cells, which may be the key to causing severe diarrhoea. Understanding these fundamental mechanisms is crucial to preventing long-lasting disease and resulting malnutrition.”

Convergent evolution: similar mechanisms in bacteria and parasites

Cryptosporidium isn’t the only pathogen known to cause microvilli elongation in the intestine. A type of E. coli also infects the intestine and causes diarrhoea. This type of E. coli is also known to drive microvilli elongation, by the action of a protein called Map that manipulates structural proteins within intestinal epithelial cells during an infection.  

Surprisingly, the team found that MVP1 of Cryptosporidium interacts with the same structural proteins as Map of E. Coli, EBP50 and CDC42. The team believes this is a unique occurrence of convergent evolution, where proteins causing disease in infectious bacteria and parasites have independently evolved to have the same function.  

Elena Rodrigues, former PhD student in the Cryptosporidiosis Laboratory at the Crick, said: “The similarities in effector proteins between a type of E. Coli and Cryptosporidium show a fascinating example of convergent evolution: how pathogens from two different kingdoms of life have separately evolved proteins that have the same effect on the host. Although more research is needed to understand exactly how Cryptosporidium causes diarrhoea through these mechanisms, our work is a solid foundation.”

Reference: Rodrigues E, Pallett MA, Straker LC, et al. Cryptosporidium modifies intestinal microvilli through an exported virulence factor. Cell Host & Microbe. Published online April 28, 2025. doi:10.1016/j.chom.2025.04.001

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.