Targeting a waterborne foe

Apr 25, 2010

Discovered in 1976, cryptosporidium lurks worldwide in water, contaminating swimming pools, water parks, and drinking water supplies. Although it has even been featured on the comedy show The Colbert Report, it is no laughing matter—this microscopic pathogen is a leading cause of diarrhea and malnutrition and the most common source of infection in immune-weakened people such as AIDS patients. It is also a potential bioterrorism agent.

"All you need is a cow and a centrifuge to harvest enough oocysts to infect a small city," says Brandeis University biochemist Liz Hedstrom. Roughly 20 percent of calves are infected by cryptosporidium oocysts, which are found in their feces. In 1993, in the largest waterborne disease outbreak in U.S. history, this nasty infiltrated Milwaukee's municipal water supply, killing more than 100 people and sickening some 400,000.

Cryptosporidium invades the , where it opens fire, typically causing severe gastrointestinal distress and even death in people with weakened immune systems. Cryptosporidium is a hardy foe whose oocysts—a spore-like phase in the parasite life cycle—remain stable outside a host for long periods and are resistant to conventional water treatment such as chlorine disinfection.

The latest research news on this waterborne foe will be the focus of Hedstrom's talk, titled "Targeting a prokaryotic protein in a eukaryotic parasite," at the American Society for Biochemistry and Molecular Biology's annual meeting. Hedstrom's promising research could lead to an effective treatment to prevent cryptosporidiosis.

Hedstrom and her collaborators made a critical breakthrough in eroding cryptosporidium defenses when they identified IMPDH, a key enzyme involved in the biosynthesis of RNA and DNA, as a potential . Her research has shown that IMPDH inhibitors block the parasite from proliferating in vitro. Importantly, the Cryptosporidium IMPDH has very different properties from those of the human enzyme counterpart.

Next, Hedstrom and her colleagues identified compounds that blocked the action of the Cryptosporidium IMPDH, but spared human IMPDH. Leading a large-scale screen of a commercial library containing 129,000 compounds, Hedstrom discovered more than fifty compounds that specifically inhibit the parasite enzyme. A number of these compounds display antiparasitic activity. Hedstrom is now working on improving the compounds' potency, bioavailability and metabolic stability, a first step in the drug development process.

"It's a difficult problem, but we think that we have some very promising compounds," says Hedstrom.

Explore further: Two-armed control of ATR, a master regulator of the DNA damage checkpoint

add to favorites email to friend print save as pdf

Related Stories

Stomach illness outbreak in Colorado

Sep 04, 2007

Colorado authorities are trying to identify the sources of a large outbreak of cryptosporidiosis, a stomach illness caused by a microscopic parasite.

Ultraviolet light helps to secure water supply

Oct 18, 2007

A major public health issue and economic problem has been addressed in experiments carried out by researchers from the University Denis Diderot in Paris, and the VEOLIA Research Center in Maisons-Laffitte (France).

Gene targeting discovery opens door for vaccines and drugs

Apr 13, 2009

In a genetic leap that could help fast track vaccine and drug development to prevent or tame serious global diseases, DMS researchers have discovered how to destroy a key DNA pathway in a wily and widespread human parasite. ...

Recommended for you

Japanese scientist resigns over stem cell scandal

12 hours ago

A researcher embroiled in a fabrication scandal that has rocked Japan's scientific establishment said Friday she would resign after failing to reproduce results of what was once billed as a ground-breaking study on ...

'Hairclip' protein mechanism explained

Dec 18, 2014

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.