U of M researchers discover genetic key to treating deadly fungal infections

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U of M researchers discover genetic key to treating deadly fungal

infections

http://www.eurekalert.org/pub_releases/2006-07/uom-uom071706.php

Contact: Mark Cassutt

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University of Minnesota

University of Minnesota researchers have discovered how a prevalent

fungal pathogen that causes 10,000 deaths per year in the United

States overcomes the effects of antifungal drugs by duplicating a

section of one of its chromosomes.

Candida albicans, a type of yeast present in 80 percent of humans,

is usually harmless. In otherwise healthy people, it can cause mild

oral and vaginal infections (candiasis or thrush) that are easily

treated. But in people whose immune systems are suppressed (by AIDS,

chemotherapy, or drugs for surgery or organ transplantation) it can

produce deadly, systemic infections, causing death in 30 to 50

percent of cases. Premature babies, whose immune systems are

immature, are also at risk.

Led by Judith Berman, professor of genetics, cell biology and

development, university researchers have discovered that C. albicans

can neutralize an antifungal drug by modifying one of its own

chromosomes. The cell duplicates one arm of chromosome 5 and deletes

the other, replacing it with the duplicate arm. The altered

chromosome is known as an " isochromosome. " The effect of the

duplication is to help the cell tolerate the antifungal drug, thus

allowing the yeast to continue growing despite the presence of the

drug.

The discovery, which is reported in the July 21 issue of Science,

could lead to strategies for making currently available antifungal

drugs more effective.

" This creates important clinical opportunities, " said Berman. " The

next step is to find a companion drug to block the formation of

isochromosomes during antifungal treatment. "

Berman also explained that some cancerous tumors contain

isochromosomes, which means that the finding may yield clues about

how some tumors become resistant to chemotherapy and how researchers

can develop companion drugs that inhibit the development of that

resistance.

About 25,000 Americans develop these fungal infections each year.

And in spite of treatment with antifungal drugs, 10,000 die. The

number of hospital-acquired C. albicans infections is increasing.

There are few drugs available to treat it and the fungus often

becomes resistant to a drug, making it ineffective. The cost to the

U.S. health care industry is $1 billion per year.

Berman explained that drugs that are toxic to fungi are often toxic

to humans. Thus, anti-fungal drugs are usually intended to suppress,

rather than kill, C. albicans. This suppression encourages the

organism to evolve resistance to the drug in order to survive.

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The university's department of genetics, cell biology and

development is jointly administered by the College of Biological

Sciences and the Medical School.

Faculty in the College of Biological Sciences conduct research that

ranges from molecules to ecosystems and from human to environmental

health.