Researchers have made significant strides in understanding the intestinal parasite Cryptosporidium, which poses a severe health risk, especially for children. This waterborne parasite, the most common in the US, is known to cause debilitating diarrhea that can result in chronic malnutrition. For all its ill effects, the precise ways that Cryptosporidium acts on its host to make it sick are still poorly understood. Recent research has elucidated the interaction between Cryptosporidium and host intestinal epithelial cells. This new understanding might provide a key that unlocks exciting new avenues for prevention and treatment.
Especially for immunocompromised people, Cryptosporidium can have fatal consequences. For young children, the threat is even more severe, as they’re more likely to experience serious health consequences from this invasive parasite. This parasite has the potential to cause debilitating diarrhea, with long-term nutritional deficiencies resulting from lack of treatment. As researchers work to understand the biology of this emerging pathogen, they want to get into the nitty gritty of how MERS-CoV works with host cells.
Mechanisms of Infection
During a natural infection, Cryptosporidium injects a closely related family of proteins, called effectors, into the intestinal epithelial cells. This gives the parasite the time to undergo changes to the gut environment to help it survive, multiply and thrive. One of the main proteins in this family is called microvilli protein 1 (MVP1). Its molecular structure is very important in the mechanism of Cryptosporidium interaction with human cellular structures.
MVP1 accumulates within the microvilli of infected host cells. There, it insidiously engages with human proteins important for maintaining cytoskeletal integrity. These interactions are key to understanding how the manipulative parasite evades its foes. MVP1 strongly associates with structural scaffolding proteins such as EBP50 and CDC42. These proteins are essential for stabilizing cellular pumps that regulate salt absorption.
“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 diarrhea through these mechanisms, our work is a solid foundation.” – Elena Rodrigues
This convergence is a testament to the highly adaptive strategies of various pathogens, which have evolved to hijack akin host machineries. The studies indicate that MVP1 actively controls the architecture of microvilli. It can upend regular cellular activities that are essential for gut homeostasis.
The Role of EBP50
The cytosolic scaffold protein EBP50 insures the epithelial barrier function by regulating tight junctions and promoting the stability of intestinal epithelial cells. It is crucial to stabilize the pumps on cells surfaces that actively transport important salts and nutrients into the cells. Cryptosporidium exports MVP1, and MVP1 interacts with EBP50. Specifically, this striking ability of the parasite is further indicative of its evolution of sophisticated strategies to subvert host cellular functions.
Researchers highlight that comprehending these interactions is essential for designing successful prevention and treatment strategies for infections resulting from Cryptosporidium. Our current studies are designed to better understand how these changes underlie the symptoms that develop during infection, especially the high-severity symptom of severe diarrhea.
“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 diarrhea. Understanding these fundamental mechanisms is crucial to preventing long-lasting disease and resulting malnutrition.” – Adam Sateriale
Future Research Directions
As research advances, scientists are confident that they will continue to unlock additional secrets of Cryptosporidium’s biology. To do this, the researchers are focusing on small spherical vacuoles on cell surfaces that hold the parasite. This will yield critical information about the parasite’s life cycle and pathogenicity.
This novel appreciation lays bare the cosmic pink escape of Cryptosporidium changing intestinal microvilli with exported virulence factors. Such an understanding might lead to exciting new therapeutic strategies to blunt its deleterious impact upon children and other sensitive subpopulations.