Sequencing of parasite genome could lead to life-saving treatments
By Jonathan Weil
A team of researchers, led by the University of Minnesota and Weill Cornell Medical College in New York City, has determined the complete genome sequence of Cryptosporidium, a common diarrhea-causing parasite that can lurk in drinking water. The parasite can be deadly for infants, the elderly and those with weakened immune systems, particularly AIDS patients.
"The completion of the genome sequence represents the greatest advancement in our understanding of the organism," said Dr. Thomas J. Templeton, a co-first author of the study and assistant professor of microbiology and immunology at Weill Cornell Medical College and Weill Cornell Graduate School of Medical Sciences in New York. "Currently there are no drug treatments for Cryptosporidium, and through genome sequence annotation, we have identified many new drug targets that may lead to new pharmaceuticals to treat the illness."
The finding was published in the March 25 issue of the electronic journal Science Express, to be followed by publication in April in the print version of Science.
"Cryptosporidiosis is a hard-to-treat condition, largely because we lack a basic understanding of the genetic make-up of the organism," said principal investigator Dr. Mitchell Abrahamsen of the University of Minnesota College of Veterinary Medicine and Biomedical Genomics Center, where the genome sequencing was carried out.
Cryptosporidium parvum is a protozoan and its infectious agent, called an oocyst, cannot be killed by the chlorine typically used to kill germs in drinking water. If the oocysts are swallowed, either in contaminated drinking water or food, the parasite can wreak havoc on the intestines. People with healthy immune systems can suffer from diarrhea, abdominal pain and fever, but the parasite can be deadly for those with weakened immune systems, particularly AIDS patients.
"Although healthy individuals rapidly recover from cryptosporidiosis, no drug therapy exists for treating people, and the parasite can cause an unrelenting infection in AIDS patients," said Templeton. "This is a particular problem in some parts of the world, such as Africa, where HIV drug regimens are often unavailable."
Cryptosporidium has caused huge infection outbreaks in the United States and Canada, including a 1998 outbreak involving 400 people that was traced to a diaper-contaminated drinking fountain at a Minnesota zoo. In 1993, a breakdown in a water filtration plant resulted in 400,000 cryptosporidiosis cases and 100 deaths in Milwaukee.
The parasite also has been found in contaminated ponds, lakes and swimming pools with inadequate filtration, as well as in oysters and uncooked food washed in tainted water. Although tap water generally is considered safe, officials in some cities have recommended that HIV-infected individuals, particularly those with weaker immune systems, boil tap water to eliminate the risk of cryptosporidiosis.
Despite the risk to humans, Cryptosporidium has proven difficult to study. The parasite lurks inside cells of the gastrointestinal system during one stage of development, an environment that is hard to replicate. The organism cannot be propagated continuously in the laboratory and, therefore, cannot be genetically manipulated, said Templeton.
In the Science study, Templeton and a team of University of Minnesota researchers, led by Abrahamsen, studied Cryptosporidium DNA collected from oocysts found in the feces of infected calves. Genetic sequencing revealed a relatively pared-down organism with only 9 million DNA base-pairs, the building blocks of DNA, and eight chromosomes, the tightly coiled packets of DNA.
The researchers found the germ lacks some essential structures found in bacteria and other parasites. For example, Cryptosporidium lacks functioning mitochondria, the energy-generating structures found in most cells. This leaves the germ completely dependent on its host for nutrition.
"Cryptosporidium is an extreme parasite, in that it has a highly streamlined metabolism and cellular structure that makes its survival dependent on the cells lining the intestines," said Templeton. "We hope to take advantage of that fact and find drugs that can halt the parasite."
The researchers have identified several unique enzymes and novel cell-surface and secreted proteins that could be potential Achilles heels for Cryptosporidium, according to the report.
The study's co-authors are from Tufts University, Texas A&M University, Virginia Commonwealth University and the National Center for Biotechnology at the National Institutes of Health (NIH).
The study was funded by the National Institute of Allergy and Infectious Diseases at NIH.
Originally published in the April 22, 2004 issue of Cornell Chronicle
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