Cryptococcus neoformans

NIH, NIAID Want More Info on Fungus Among Us

The National Institutes of Health recently classified fungi as a source of emerging infectious diseases requiring new attention, which is a direction Dr. Christina Hull was already pursuing. A fungus expert at the University of Wisconsin-Madison, Hull recently received a five-year, $1.8 million grant from the National Institute of Allergy and Infectious Diseases to study how Cryptococcus causes disease.

While not necessarily a household word yet, "Cryptococcus" has been on the general media radar for at least a decade, ever since the fungus species known as Cryptococcus gattii was first noticed in British Columbia in 1999. The microbe is normally found in the bark of eucalyptus trees in Australia and other tropical zones, but by 2000 it became clear to physicians and veterinarians that its presence in North America was no anomaly. Like the bird flu and West Nile Virus, it can affect both animals and humans who are otherwise healthy.

In the past decade, Cryptococcus gattii has crept into Washington state and Oregon, and scientists predict it may soon spread to California and other neighboring areas. Several people in Oregon have died after being infected with the new VGIIc genotype of the species. In the 21 Pacific Northwest cases analyzed by researchers, the strain has a death rate of about 25 percent.

Hull, an assistant professor of biomolecular chemistry in the School of Medicine and Public Health, has studied fungi for years. She notes that Cryptococcus neoformans, a species related to C. gattii, shows up in humans through pneumonia when immune systems are weak, most typically in patients with AIDS or those who have received organ transplants or are on cancer chemotherapy. "Most healthy people don't show any symptoms," she notes of C. neoformans. "The fungus is inhaled into the lungs of people who may have been near trees or soil where the microbes live."

Cryptococcus can cause persistent coughing, chest pain, shortness of breath, and fever -- symptoms that can appear two to several months after exposure. The microbes can pass from the lungs into the central nervous system, where they can cause meningitis. The fungus does not spread from human to human, adds Hull, who also is a faculty member in the Department of Medical Microbiology and Immunology. She says, however, that unlike C. neoformans, C. gattii causes disease in healthy people, even though the numbers are small.

"At its peak on Vancouver Island, Cryptococcus gattii caused disease in 218 people, killing nine percent of them," she says. Some people think the species may have traveled south on logging trucks or car tires.

"It has adapted to the new environment," Hull says.

Antifungal medications are fairly effective for most people. But Hull hopes that her research will lead eventually to treatments for people with compromised immune systems as well as for the healthy people who sometimes get sick. Usually, the infections can be treated, but there is no vaccine to prevent them.

"First we need to learn how these complex microorganisms develop and cause human disease," Hull says. "Understanding the basic biology of Cryptococcus species will also help in the development of more effective means of preventing and treating fungal diseases in general."

Aspergillus, Blastomycetes, Histoplasmosis, Coccidioides, and Candida are examples of other fungi that cause disease in humans with varying degrees of severity.

In addition to studying the basic biology of Cryptococcus, Hull's team focuses on spores, the reproductive parts of the fungus that are highly resistant to environmental changes.

"We think spores may be the infectious particles that invade the lungs," she says. Her group recently succeeded in purifying and producing large quantities of spores, a first-time achievement that now allows the scientists to examine exactly how spores affect the immune systems of laboratory animals. The team's genetic studies are showing that some genes work only in spores or only during germination, when they are growing.

"These genes are excellent candidates for studies to determine which genes are important for regulating fungus growth in mammalian lungs," Hull says.

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