Study assesses virulence of Cryptococcus strains, laying groundwork for improved treatment

The laboratory of Kirsten Nielsen in the Center for One Health Research has taken a step toward improved treatment of Cryptococcus, completing a six-year study to examine the virulence of 38 clinical isolates from various strains of Cryptococcus. The results are published in Nature Communications.

"The question that we've been addressing is: Can we predict severe disease outcomes in patients?" said Nielsen, professor of microbiology and immunology in the Virginia-Maryland College of Veterinary Medicine. "If we can predict disease outcome then we can treat patients better. In these studies, we identified not just the genes that allow Cryptococcus to cause disease, but also the gene alleles that allow it to cause more disease or less disease."

Cryptococcus neoformans is a type of fungus that can cause serious infections in humans and many animal species. It's commonly found in the environment, especially in soil contaminated with bird droppings. When a person inhales the microscopic spores of Cryptococcus, it can lead to an infection called cryptococcosis. This infection often affects the lungs and can spread to the brain. People with compromised immune systems, such as those with HIV/AIDS or organ transplant recipients, are at higher risk.

"We're setting the foundation for future treatments," Nielsen said. "Once we understand the biology of the infection, and how it is influenced by different Cryptococcus gene alleles, then we can develop new treatments targeting these genes."

Nielsen came to Virginia Tech this fall after 17 years at the University of Minnesota. She brought $8 million worth of NIH grants to her new lab at COHR. One of those grants supported this most recent research finding.

COHR is a collaboration between the Virginia-Maryland College of Veterinary Medicine and the Edward Via College of Osteopathic Medicine, founded on the principles of One Health, the philosophy that human, animal, and environmental health are inextricably linked.

Nielsen said that the entire genome of each strain was sequenced to find what genes were associated with varying intensities of disease in a mouse model that mimics human disease. The work of further identifying disease impacts and their genetic causes and, potentially, improved treatments for disease will move forward from this study.

"Some of our African collaborators are going to develop diagnostic tests that will identify the allele differences in the genes that we've identified. The hope is that these diagnostic tests can be used in the clinic to predict disease severity and how that should affect treatment strategy," Nielsen said. "My group is also going to be looking more closely at the function of the genes we've identified and how they are influencing disease."