Tufts Veterinary School Scientists Decode Cryptosporidium Genome

NORTH GRAFTON -- A team of scientists at Tufts University School of Veterinary Medicine has helped decode the genome sequence of Cryptosporidium hominis, an insidious parasite identified as one of the most common causes of waterborne diseases in humans and classified by the Centers for Disease Control and Prevention (CDC) as a potential bioterrorist agent. The researchers' findings are reported in the journal Nature.

Cryptosporidium hominis is a highly contagious parasite that lives in the intestines of infected humans. Since there are no effective treatments, it is a relentless public health concern.

"Sequencing the genome of Cryptosporidium will help us determine the underlying mechanisms of the organism's unusual resistance to antimicrobial agents, and enable us to develop preventive vaccines and/or pharmaceutical treatments," said Saul Tzipori, PhD, director of Tufts' division of infectious diseases and a member of the multi-institutional team researching the genome.

Present in drinking and recreational water throughout the world, Cryptosporidium causes watery diarrhea that can lead to dehydration, weight loss, stomach cramps, fever, nausea, and vomiting. While healthy people usually overcome illnesses caused by the organism, it can be life threatening to malnourished children and people whose immune systems have been compromised because of cancer, AIDS, etc.

The Cryptosporidium pathogen, which can be found in the feces of both humans and animals, is difficult to work with, thereby impeding the efforts of investigators to conduct laboratory investigations and develop appropriate therapies.

Tufts researchers successfully isolated and propagated Cryptosporidium hominis in 2000, making Tufts the first research institution capable of propagating this pathogen.

In 2000, Tufts applied to the National Institutes of Health (NIH) for funding to enable a consortium of researchers at Tufts, Virginia Commonwealth University and the University of Minnesota to simultaneously sequence the genomes of two Cryptosporidium pathogens infectious to humans -- Cryptosporidium hominis and Cryptosporidium parvum.

The article in Nature describes the consortium's successful decoding of Cryptosporidium hominis -- one of the two pathogens found in humans. In addition to producing DNA from the Cryptosporidium hominis isolate TU502, Tufts scientists constructed a bacterial artificial chromosome library for this research project. "This library is important for building a scaffold of the genome, on which the smaller sequence assemblies are aligned," said Giovanni Widmer, PhD, associate professor in Tufts' department of biomedical sciences and a lead author of this study.

In April 2004, the consortium announced in the journal Science that it had successfully sequenced the eight chromosomes found in the genome Cryptosporidium parvum, the pathogen found in ruminants and humans.

"What is unique about this project is that the genomes of two related human and veterinary pathogens were sequenced in parallel," Widmer said. "This now puts us in a position to not only identify potential drug and vaccine targets, but also unravel key biological characteristics that might help explain the difference between the pathogen that infects humans only and C. parvum, which is transmitted between humans and animals."

Source: Tufts University