Contacts: Judith Berman, Ph.D., (612) 625-1971Deane Morrison, University News Service, (612) 624-2346
POTENTIAL ACHILLES HEEL FOUND IN INFECTIOUS YEAST
MINNEAPOLIS / ST. PAUL--A research team led by a University of Minnesota geneticist has found a gene in yeast that is essential for yeast cells to change their shape, a property necessary for them to become infectious. The gene codes for a protein that allows the infectious yeast, Candida albicans, to grow filaments that invade human tissue, causing not only nuisance infections but death in 30 percent of vulnerable patients who suffer systemic infections. The work is featured on the cover of the current issue of the journal Molecular and Cellular Biology.
"This work suggests that we can use a noninfectious yeast to identify proteins important in changing cell shape that may be promising targets for antiyeast drugs," said lead investigator Judith Berman, a professor of genetics, cell biology and development and also of microbiology at the university.
Although Candida albicans is the infectious species of yeast, it is a difficult subject for genetic experiments. Therefore, the research team worked largely with baker's yeast, which does not normally form filaments that can invade human tissue. The scientists transferred a Candida gene called INT1, which helps such filaments to form, from Candida to baker's yeast. The researchers found that INT1 induced the formation of filaments in baker's yeast, just as it does in Candida. But in order to do so, it required a baker's yeast gene called SLA2. The researchers found that Candida has an SLA2 gene as well, and discovered that if that gene is disabled, Candida cannot form filaments.
"If it can't form filaments, the yeast can still survive as round, budding cells," said Berman. "But it can't invade tissues effectively. Thus, it is unlikely to be pathogenic."
The SLA2 gene is necessary for Candida cells to maintain a structure known as the actin cytoskeleton, which is a framework of tiny protein tubes that push the cell into new shapes such as filaments. The gene provides the blueprint for a protein that has no clear counterpart in humans. This makes it a potential target for therapeutic agents because drugs directed against it would not likely interfere with any human proteins.
The work was supported by Burroughs Wellcome Fund and the National Institutes of Health.
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