VCU scientist decodes genome of potential bioterror agent

By Anne Buckley and Sathya Achia Abraham

RICHMOND, Va. (Oct. 27, 2004) – The genome sequence of a dangerous parasite with bioterrorism potential has been decoded, enabling scientists to better understand the organism and work to develop vaccines and therapeutic drugs, a Virginia Commonwealth University scientist said in Thursday’s issue of the journal Nature.

Decoding Cryptosporidium hominis permits researchers to understand its complex life cycle, its ability to survive in diverse environments and its ability to invade its host and cause disease. Scientists will now use that critical information to develop methods to protect against cryptosporidiosis, the disease the parasite causes, wrote Gregory A. Buck, Ph.D., director of the Center for the Study of Biological Complexity at VCU.

“The genome sequence of the organism provides us with candidates for the proverbial ‘Achilles heel’ of the parasite,” said Buck, a professor in microbiology and immunology. “Since the genome was decoded, we have already identified several hundred previously unknown potential vaccine and drug targets encoded in the genome.

“This presents an unprecedented opportunity to combat this disease, for which there is currently no therapy available,” he said.

The single-celled, parasitic protozoan brings on a severe watery diarrhea in humans. Over the last decade, cryptosporidiosis has become a primary recognized cause of waterborne illness in the United States and throughout the world. In 1993, Milwaukee experienced the largest recorded outbreak of the waterborne disease when more than 400,000 people became ill and more than 100 died.

The Centers for Disease Control and Prevention has classified Cryptosporidium as a potential bioterrorism agent because it is highly infectious, very difficult to control and there is no therapy for it.

Cryptosporidium is transmitted by the ingestion of oocysts, the infective stage of the organism, which completes its life cycle once inside its host. Oocysts have tough protective walls, allowing them to survive under a wide range of environmental conditions. The parasite is resistant to chemical disinfectants like chlorine that are used in water treatment. Elimination from water supplies requires physical means such as filtration.

 “Cryptosporidia can contaminate public drinking water supplies by exposure to waste from human or animal carriers,” said Buck. “Once contaminated, water supplies are extremely difficult and expensive to clean up because the organism is refractory to normal water treatment procedures.

"Significant contamination could be catastrophic for a city or other municipality,” Buck said.

The protein-coding genes of C. hominis indicate that the organism has a highly tailored glycolysis-based metabolism; is dependent on its host for nutrients; and that it has adopted an unusual two-stage life cycle, according to the article.

The C. hominis research was part of a $5.5 million, multi-institutional genome decoding project that also included investigators at the University of Virginia, Tufts University and the University of Minnesota. More information can be found at www.hominis.mic.vcu.edu.

VCU researchers are now applying the genome data in a $1 million project to develop vaccines against Cryptosporidium, and in a $2 million project to dissect the gene expression programs responsible for pathogenesis of the parasite. The vaccine project is part of a national consortium of biomedical research institutions established by the U.S. Department of Health and Human Services to help fight bioterrorism.