Researchers Unlock Genetic Code of Dangerous Parasite

Could lead to drugs to treat germ that threatens those with weak immune systems

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By
HealthDay Reporter

THURSDAY, March 25, 2004 (HealthDayNews) -- Scientists have sequenced the genome of Cryptosporidium parvum, an intestinal parasite that is particularly harmful to people who have weakened immune systems.

The sequencing revealed several Achilles' heels in the structure of crypto, as the bacterium is known, that could be potential drug targets.

So far, this particular parasite has eluded all attempts to crush it with medication.

"I think the genome sequence is a huge step forward for people studying this genome, and it is obviously going to provide an excellent resource for those looking for new drug targets and vaccines," says Neil Hall, an assistant investigator at the Institute for Genomic Research. Hall was one of the main authors of a 2002 study that sequenced Plasmodium falciparum, which causes human malaria. The malaria parasite is closely related to Cryptosporidium parvum.

Crypto infects various animals in addition to humans. The two main routes to people are through contaminated food and drinking water. Generally, both the food and water have been in contact with infected livestock.

"This truly is a serious problem from the standpoint of water-borne and foodborne pathogens," says Mitchell S. Abrahamsen, lead author of the study detailing the findings in the March 26 issue of Science. "That's one of the other reasons we have an interest in getting the sequence, better diagnostics and ways to inactivate the parasite in water. It's a big safety issue." Abrahamsen is an associate professor at the University of Minnesota in Minneapolis.

The parasite can cause diarrhea in a healthy person and can be life-threatening in those with compromised immune systems, such as AIDS patients and individuals undergoing chemotherapy for cancer. The U.S. government considers it a "category B" biodefense pathogen, meaning the microorganism poses a potential threat as a bioterrorist weapon.

Despite two decades of research, there are no drugs to treat the infection and no ways to prevent it. The reason has to do with the basic biology of crypto.

Antibiotics, which are used against bacteria, target biochemical pathways in those organisms that don't exist in humans. That way, the drugs harm the bacteria while sparing people.

The problem with crypto and its cousin, malaria, is that their biology is closer to that of mammals than the average bacteria. "It's difficult to find biochemical pathways [as targets] in parasites because parasites and fungi are more similar to mammals than bacteria are," Abrahamsen explains. "We tried to identify biochemical pathways that would be unique to crypto."

And they found some. "There are a lot of pathways crypto has that look more similar to bacteria and plants than humans, and those should be nice pathways to target," Abrahamsen says.

New drugs won't develop overnight.

"The findings in the paper are a start, although it is not at all unusual for a genome project to throw up some unexpected or divergent enzymes and pathways," Hall says. "In fact, it is a feature of parasites that no two are the same, as their metabolism reflects their environmental niche, which is usually pretty specific."

"I expect that we will see a flood of more detailed analysis soon, along with many functional genomic studies," Hall adds. "Now that Cryptosporidium is officially a biodefense-related organism, we can expect plenty of NIAID money to be directed toward interpreting the genome." NIAID is the National Institute of Allergy and Infectious Diseases.

But the new findings offer more implications for pure science. Crypto is related to malaria and also to toxoplasma, all of which are included in the group of parasites called Apicomplexa.

"Now that we have found the genome for malaria and crypto, we should be able to start understanding the unique biology of this group of parasites," Abrahamsen says. "It should provide a lot of insights into how they evolved into pathogens. And, by looking at malaria, which is in the blood, and crypto, which is intestinal, and look at the differences, we should start to understand the biology that allows them to occupy different niches within their human hosts."

More information

For more on crypto, visit Ohio State University or the U.S. Food and Drug Administration.

SOURCES: Mitchell S. Abrahamsen, Ph.D., associate professor, University of Minnesota, Minneapolis; Neil Hall, Ph.D., assistant investigator, The Institute for Genomic Research, Rockville, Md.; March 26, 2004, Science

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