Searching for a solution to a deadly pathogen

Cryptosporidium is a microscopic pathogen that finds its way into various water sources like swimming pools, water parks, and drinking water supplies due to fecal contamination from humans and animals. Discovered in 1976, Cryptosporidium, also known as “crypto,” contaminates these water sources and is one of the leading causes of diarrhea and malnutrition worldwide.

In the largest waterborne disease outbreak in U.S. history, Cryptosporidium infiltrated Milwaukee’s municipal water supply in 1993, killing more than 100 people and sickening some 400,000. The parasite is now recognized as a major cause of waterborne disease.

Cryptosporidium is a resilient parasite whose oocysts – a spore-like phase in the parasite life cycle – remain stable outside of a host for long periods and are resistant to conventional water treatment such as chlorine disinfection. As water supplies are contaminated with the pathogen and consequently ingested by people, Cryptosporidium invades the small intestine typically causing severe gastrointestinal distress and even death in people with weakened immune systems. One of the concerns is the lack of a therapeutic treatment for the disease.

A recent study by Dr. Hedstrom and her researchers titled, The Structural Basis of Cryptosporidium-Specific IMP Dehydrogenase Inhibitor Selectivity published by the Journal of the American Chemical Society have reported a critical breakthrough in penetratingCryptosporidium defenses when they identified IMPDH, a key enzyme involved in the biosynthesis of RNA and DNA, as a potential drug target. Their research has shown that IMPDH inhibitors block the parasite from proliferating in vitro (in the host).

Importantly, the Cryptosporidium IMPDH has very different properties from those of the human enzyme counterpart. Hedstrom and her colleagues identified compounds that blocked the action of the Cryptosporidium IMPDH, but spared human IMPDH. Dr. Hedstrom’s pioneering research is the first step in the drug development process and could lead to the first effective treatment in preventing Cryptosporidium infection.

(Joan Rose, PhD, is the Homer Nowlin Chair in Water Research at Michigan State University and a member of the Water Quality & Health Council.)

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