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Research Turns the Tide on Water-borne Pathogen </b>
Rose Hoban
February 5, 2008

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Cryptosporidium is a water-borne parasite that's responsible for many of the cases of diarrhea that affect children in the developing world. In more developed countries, cryptosporidium is often a problem for people who have compromised immune systems, such as those with AIDS or cancer. Rose Hoban reports on a new development in combating the pathogen.

Researcher Liz Hedstrom from Brandeis University in Massachusetts says the drugs currently available for treating cryptosporidium are not very effective. There are no vaccines against the microbe.

Hedstrom says there's a reason for that: cryptosporidium is a eukaryotic parasite. That means its proteins are quite similar to human proteins. "That actually makes it hard to develop a drug," she explains.

She says there are few chemical compounds that work well against cryptosporidium without making their human hosts sick. In addition, Hedstrom says, the parasite is difficult, if not impossible, to grow in a lab.

But researchers recently sequenced cryptosporidium's DNA. Hedstrom and her colleagues made use of that information. "So from that, we could make a good guess about how cryptosporidium grows," she says, "what sort of food it needs to eat, how it metabolizes its food into... say, DNA, RNA, the things it needs to proliferate."

From that, Hedstrom and colleagues from the University of Georgia could make a hypothesis about which proteins were crucial for the growth and the reproduction of the parasite.

They isolated a specific enzyme the cryptosporidium must make in order to survive. Then they screened about 40,000 different chemical compounds to see if anything worked to inhibit the production of this enzyme.

"We found 10 compounds that did selectively bind to the parasite enzyme and not the human version," Hedstrom says. "It turns out that those 10 compounds do actually inhibit parasite growth."

The next step, Hedstrom says, is to test these ten compounds to see which works best and can be tolerated by animals and then by humans. She hopes that in several years, they'll be testing prototype drugs in animals.

Her research is published in the journal Chemistry and Biology.



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