Deadly human pathogen Cryptococcus fully sequenced

Now researchers have sequenced the entire genome and all the RNA products of the most important pathogenic lineage of Cryptococcus neoformans, a strain called H99.

The results, which appear April 17 in PLOS Genetics, also describe a number of genetic changes that can occur after laboratory handling of H99 that make it more susceptible to stress, hamper its ability to sexually reproduce and render it less virulent.

The study provides a playbook that can be used to understand how the pathogen causes disease and develop methods to keep it from evolving into even deadlier strains.

"We are beginning to get a grasp on what makes this organism tick. By having a carefully annotated genome of H99, we can investigate how this and similar organisms can change and mutate and begin to understand why they aren't easily killed by antifungal medications," said study coauthor John Perfect, M.D., a professor of medicine at Duke who first isolated H99 from a patient with cryptococcal meningitis 36 years ago.

The fungus Cryptococcus neoformans is a major human pathogen that primarily infects individuals with compromised immune systems, such as patients undergoing transplant or those afflicted with HIV/AIDS. Researchers have spent many years conducting genetic, molecular and virulence studies on Cryptococcus neoformans, focusing almost exclusively on the H99 strain originally isolated at Duke. Interestingly, investigators have noticed that over time, the strain became less and less virulent as they grew it in the laboratory.