Virulent Parasite Yields Genetic Secrets

Cryptosporidium decoding could prevent illness, bioterrorism

WEDNESDAY, Oct. 27, 2004 (HealthDayNews) -- Researchers say they have mapped the genome for Cryptosporidium hominis, paving the way for drugs that might someday prevent or treat severe gastrointestinal illness associated with the water-borne parasite.

The achievement might even have implications for the fight against bioterrorism, experts say, since U.S. health officials now classify the parasite as a "category B" organism that could be dumped into public water supplies.

"It's very infectious, easy to pass from one person to another," said lead researcher Dr. Gregory A. Buck, a professor of microbiology and immunology at Virginia Commonwealth University. "It's also very difficult to clean Cryptosporidium out of the water supply once it's there."

Until now, however, it's been tough to conduct research on the organism, because it's so difficult to cultivate in the laboratory.

The genome discovery should change all that, Buck said.

"What we've been able to do over the past 12 months is define Cryptosporidium's physiology and biology, based on comparative genomics," he said. "Looking at genes that it has or doesn't have, we can find out what it needs to live on, how it makes its energy, the whole physiology of the organism."

Details of the C. hominis genome -- which is comprised of 9.2 million base pairs of DNA -- appear in the Oct. 28 issue of Nature.

Infection with the single-cell Cryptosporidium parasite can cause nausea and diarrhea lasting for days. It's especially prevalent -- and lethal -- in contaminated water supplies in the developing world, where it is estimated to cause 25 percent of childhood diarrheas, a major killer.

But the bug doesn't restrict itself to poorer nations. "There are outbreaks in the United States all the time," Buck said. "The biggest one was in Milwaukee in 1993 -- 400,000 people were infected. One hundred and twelve people died, mainly individuals with compromised immune systems, such as people with HIV."

Despite its prevalence, science has had a tough time recreating C. hominis for study in the lab. "It's been very, very hard to get any of this organism to study," Buck said. "In fact, that was the justification we placed in front of the National Institutes of Health, and they gave us the money for this project."

The genome has yielded some surprises, as well as potential targets for drug therapy. According to Buck, C. hominis differs from other parasites in that it relies on the human host cell for many normal cellular functions.

"For example, it can't make its own amino acids from precursor molecules," Buck said. "That's really important, because amino acids are the building blocks of protein, which are the business ends of cells -- they do all the work."

Instead, the parasite uses transporter molecules to import amino acids from outside the cell. "Now, if we can find a drug that blocks the transport of the precursors for those amino acids from getting into the C. hominis cell, the cell will die," he said.

Vaccine therapy will also be accelerated by the mapping of the genome, he said, as scientists identify C. hominis proteins that might be used to prime the body's immune system to fight the bug.

Such a vaccine might be especially useful in a counter-bioterrorism setting, Buck said, where it might be used to immunize troops against drinking water known to be contaminated with Cryptosporidium.

Neil Hall, a researcher at the Institute for Genomic Research, said the genome decoding will now allow scientists "to design drugs in a rational way, rather than relying on luck."

"For any organism that is a human pathogen, it's a vital tool kit," he said.

But he cautioned that, even with a full genome available, the process of drug discovery is a long one. "To have something on the shelf that people could get prescribed, or something you might buy over the counter, that could take 10 years," he said.

More information

To learn more about the Cryptosporidium hominis genome, visit the Center for the Study of Biological Complexity.

SOURCES: Gregory A. Buck, Ph.D., director, Center for the Study of Biological Complexity, and professor, microbiology and immunology, Virginia Commonwealth University, Richmond; Neil Hall, Ph.D., assistant investigator, Institute for Genomic Research, Rockville, Md.; Oct. 28, 2004, Nature
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