Scientists crack genome sequence of a major parasitic pathogen

Global health threat Cryptosporidium parvum affects humans and animals

University of Minnesota researchers have completed sequencing the genome of an intestinal parasite that affects healthy humans and animals and that can be fatal to those with compromised immune systems, such as AIDS patients. The results will be published in the journal Science on March 25.

The parasite, Cryptosporidium parvum, is considered a major public health threat for which there is currently no known treatment or prevention. The gene sequencing will allow researchers to develop new ways of early diagnosis, prevention, and treatment of this parasite.

“This is a horrible, hard to treat condition, largely because we lack a basic understanding of the genetic makeup of the organism,” said Mitchell Abrahamsen, Ph.D., principal investigator, and faculty member of the University of Minnesota College Veterinary Medicine. “In fact, since analyzing the complete genome sequence, we now realize that many of the conventional antiparasitic drugs that have been used in an attempt to treat infected individuals have failed because the biochemical targets of the drugs are absent in C. parvum.”

Cryptosporidum is spread through feces of infected hosts and results in an acute case of diarrhea in humans and animals. Most people with an intact immune system recover after several days; however, for the young, elderly, and immunosuppressed individuals, symptoms can be severe and require intravenous fluid therapy to deal with the resulting dehydration.

Infection by Cryptosporidium is also one of the major causes of neonatal diarrhea in calves, contributing to significant economic loss in the dairy and beef cattle industries. In 1992, a USDA study revealed that more than 80 percent of farms surveyed were positive for Cryptosporidium.

Despite intensive efforts over the past 20 years, public health authorities have found prevention difficult. The parasite is highly resistant to environmental stresses, including chlorine treatment of community water supplies. As a result, the parasite is a significant water- and food-borne pathogen. In recent years, there have been major outbreaks of C. parvum in Milwaukee, Wis., and the Minnesota Zoo in Apple Valley.

“The genome sequence sheds new light on the genes and biochemical pathways in the parasite, and the research offers a starting point for defining the mechanisms by which the organism causes disease, and helps devise new strategies to detect, prevent, and treat C. parvum infection in humans and animals,” said Vivek Kapur, BVSc, Ph.D., co-principal investigator, faculty member of the University of Minnesota Medical School and College of Veterinary Medicine, and director of the university’s Biomedical Genomics Center and Advanced Genetic Analysis Center, where the genome sequencing was carried out.

During the sequencing project, scientists discovered several genes and unknown biochemical pathways with great similarities to bacterial and plant counterparts. “These biochemical pathways are very different from those present in humans and will provide new targets for designing effective and safe drugs against C. parvum that should have little activity or toxicity for humans,” said Abrahamsen.

The sequencing project represents part of an ambitious University of Minnesota “microbial pathogenomics” research program to sequence the genomes of a wide range of human and animal pathogens. This information then can be used to understand the mechanisms by which these pathogens cause disease.