Stemming the rising tide of yeast infections

A University study shows how infectious yeast can become drug-resistant and suggests a means to stymie such attacks

Judith Berman led a team that found how infectious yeast acquire resistance to antifungal medications. The work lays a basis for developing drugs to stymie the process.

By Deane Morrison

University researchers have discovered how the yeast that causes mild vaginal infections can become resistant to drugs, a transformation that leads to 10,000 deaths in the United States every year. Their work sets the stage for the development of new and better antifungal drugs.

The yeast, known as Candida, lives in about 80 percent of people and is normally kept in check by the immune system. But in those with immune systems weakened by AIDS, chemotherapy or immunosuppressive drugs, the yeast can produce serious infections. Doctors use the few powerful antifungal drugs in their arsenal to beat back the attack, but with drug-resistant yeast so prevalent, they lose the battle about 30 to 50 percent of the time.

Led by Judith Berman, a professor of genetics, cell biology and development, the researchers found that yeast become drug-resistant by means of a genetic trick. They published their study July 21 in the journal Science.

Berman's team discovered that resistance appears when yeast cells modify one of their chromosomes, namely, chromosome number 5. Chromosomes have two sections, called arms. The cell duplicates one arm of chromosome 5 and discards the other, replacing it with the duplicate arm. In a sense, the new chromosome is like a pencil with two eraser ends but no point. The altered chromosome, or "isochromosome," confers heightened power of resistance.

"This creates important clinical opportunities. The next step is to find a companion drug to block the formation of [modified chromosomes]."

And, as so often happens in the development of antibiotic resistance, what pushes the yeast to become resistant appears to be the drugs used to kill Candida.

"Antifungals provide the selective pressure," says Berman, meaning these drugs kill off nonresistant yeast cells, leaving the field clear for resistant cells to take over. "In the absence of a drug, cells containing isochromosomes, at least in one strain of yeast, grow less well. But in the presence of a drug, it's the other way around.

"We think there are four genes on the [duplicated] arms of chromosome 5 that [confer] resistance. Three of those genes are involved in the process by which Candida cells pump out molecules of drugs."

Preventing drug resistance in Candida is becoming more important, says Berman, because the number of hospital-acquired yeast infections is rising. Few drugs can combat Candida because the cells of yeast, unlike those of bacteria, are very similar to human cells, which makes it hard to target one without hitting the other. Accordingly, antifungal drugs are usually intended to suppress, rather than kill, the yeast. This leaves plenty of survivors, which can evolve the ability to thrive in spite of drug treatments. Thanks to these factors, Candida currently costs the U.S. health care industry about $1 billion annually.

To combat the development of drug resistance in Candida, Berman says the best approach may be to find out the exact reason why treatment with an antifungal drug should cause the yeast to rearrange its chromosomes.

"We're looking at what prompts isochromosome formation," says Berman. "This creates important clinical opportunities. The next step is to find a companion drug to block the formation of isochromosomes."

The Department of Genetics, Cell Biology and Development is shared by the College of Biological Sciences and the Medical School.

Read a news release on this research.