Scientists coax asexual yeast cells to mate
By Josephine Marcotty
Star Tribune Friday, July 14, 2000

It turns out that the nasty yeast responsible for diaper rash and many other annoying and dangerous infections in people has a secret sex life. The organism, commonly known as candida, has been studied for almost 100 years and always was believed to be asexual -- that is, its cells reproduce by splitting in two and creating exact replicas of themselves. But in a paper published today in the journal Science, researchers at the University of Minnesota confound that long-held belief by describing how they manipulated the organism into becoming two different types -- like boys and girls.

"And when you mix boys and girls you know what happens," said P.T. (Pete) Magee, the molecular biologist who coauthored the study with biologist Beatrice Magee, his wife. As a result, the scientists say they expect that they can induce the organism to produce genetically distinct offspring, which will allow them eventually to identify the genes that make it threatening to humans. That, in turn, could open the door to designing medical tools to defeat candida, which kills people 40 percent of the time that it invades their bloodstreams.

Candida occurs naturally in everyone, and infects 75 percent of women at some point in their lives as vaginitis. But it can run amok and become dangerous in those with a disabled immune system, such as AIDS and transplant patients, or anyone taking a broad range of antibiotics.

In the healthy body, both the immune system and indigenous bacteria help control candida's numbers. Because of medical advances, the populations of patients with suppressed immune systems and those who take antibiotics are rising, and as a consequence, so are the number of internal candida infections. Although it ordinarily occurs in about 8 of 100,000 people, it is far more common in seriously ill people, and is now the fourth most common infectious agent detected in the bloodstreams of hospital patients.

"Candida has evolved from being relatively unimportant in humans to being extremely important," said Dr. John Edwards, chief of infectious diseases at the Harbor-UCLA Medical Center at the University of California, Los Angeles, who is familiar with the Magees' work. Although drug treatments already exist, they are not always effective, and in some cases can be toxic to internal organs. Candida, a close relative of bakers' yeast, is also the culprit in many other irritating external infections, including the mouth infection known as thrush, and fungal infections of the skin, nails and scalp.

The Magees, who study fungi and yeast at the university, were able to make their discovery because a group of scientists at Stanford University succeeded in sequencing the candida genome. It turns out that candida has some genes that are identical to those of other fungi that are related to mating, Pete Magee said, even though it had long been believed that candida only replicated asexually. Like bacteria, each candida cell contains two copies of each of its eight chromosomes -- for a total of 16 -- and when it reproduces itself each daughter cell is an exact duplicate of the mother, he said.

In contrast, in sexual reproduction, the genetic material of two different parent organisms are mixed in the offspring. Under certain growing conditions, Pete Magee said, the candida cell loses one copy of the chromosome that contains the mating genes, leaving it with 15. The Magees were able to re-create those conditions in a lab, and found that such 15-chromosome cells somehow mated to produce offspring that contained genetic markers from each parent.

Its capacity for sexual reproduction may account for the surprisingly wide genetic variation in candida yeast, Pete Magee said, as well as its ability to develop resistance to drug treatments. Its capacity for sexual reproduction will help scientists create two lines of candida cells that are identical except for one gene. They can then test each line in animals to see precisely how that gene affects the host's life cycle, and its behavior in the host's body.

This, in turn, will allow for the development of drug treatments that disable candida's harmful affects, or for the development of a line of benign yeast that can disarm the dangerous form by mating with it, UCLA's Edwards said.

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