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Following a long-term collaborative effort, scientists have deciphered the genomes of two strains of a fungus that can lead to brain swelling and death in those with compromised immune systems. Results were published at 2 p.m. Jan. 13 in the online "express" version of the journal Science: http://www.sciencemag.org/sciencexpress/recent.shtml
The fungus, which causes severe inflammation of the brain, is called Cryptococcus neoformans (C. neoformans). It is estimated that about 15 percent of people with HIV will suffer at least one life-threatening infection; the figure may reach as high as 40 percent in Africa. Those taking chemotherapy drugs, steroid treatments or drugs to prevent rejection of a transplanted organ also are susceptible to infection.
Jennifer Lodge, Ph.D., a biochemist and associate dean of research at Saint Louis University School of Medicine, was head of the steering committee for the Cryptococcus Genome Project – a group formed in 1999 to map the genome of two common strains of this fungus. "This research will be an enormous factor in developing treatments for C. neoformans infection, which is a major problem for those with compromised immune systems," Lodge said. "We’ve discovered several unique attributes that point to new ways to attack the fungus and cure infection."
For instance, the C. neoformans develops a unique polysaccharide capsule that envelops the fungus and aids in biosynthesis. Because the study identified about 30 new genes that likely are involved in this process, scientists now could find ways to interfere with the process and stop infection. Researchers also identified differences between a highly virulent strain of C. neoformans and one that doesn’t cause severe infection. These differences may hold the key to understanding why this particular fungus is so virulent and may help to develop effective treatments. "These are just two of several exciting areas of research that now are open to scientists," Lodge said.
Brendan Loftus, a scientist at The Institute for Genomic Research (TIGR), was the first author of the paper. TIGR scientists led by primary investigator Claire M. Fraser, the President of TIGR, deciphered the genome of one strain of C. neoformans while researchers led by Richard Hyman at Stanford University’s Genome Technology Center in Palo Alto, CA, sequenced the second strain.
The project was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Numerous collaborators helped to interpret and analyze the genome sequence data, including Maureen Donlin, Ph.D., research assistant professor of biochemistry at Saint Louis University School of Medicine.
Other St. Louis scientists who participated in the research include Washington University researchers Tamara Doering, Ph.D., Michael Brent, Ph.D. and Aaron Tenney.