Studies of the reproductive behavior of a major disease-causing fungus have opened new avenues to understanding this potentially deadly microbe. In the current issue of Science, researchers from the University of Minnesota report the discovery of mating behavior in the yeast Candida albicans, an organism long thought to reproduce only by splitting itself in half. Their studies, supported by the National Institute of Allergy and Infectious Diseases (NIAID), provide new opportunities for scientists to better understand the diseases caused by this fungus.
"C. albicans has been studied for over 100 years, but it has never revealed a sexual stage in its life cycle and has defied attempts to mate," explains Dennis M. Dixon, chief of the Bacteriology and Mycology Branch of NIAID's Division of Microbiology and Infectious Diseases. "This work is extremely important because it begins to explain how the organism can adapt to changes in its environment and cause disease."
C. albicans, a common cause of thrush, can infect the skin, mucous membranes, and blood. In the latter case, the organism can invade multiple organ systems where it causes death in 30 to 50 percent of infected individuals. The fungus is particularly prevalent as a pathogen of the oral cavity and the female genital tract and as an opportunistic infection that strikes people with impaired immune systems. Existing anti-candida drugs are often highly toxic, and drug-resistant infections are becoming more common.
Unlike baker's yeast, where the genetic systems and mating have been extensively analyzed in the laboratory, C. albicans has proven difficult to study until more recently. Baker's yeast can reproduce by mating, during which two single-celled parent yeasts fuse to produce a single organism with the combined genetic material of both parents. Because C. albicans has not previously been found to mate, however, scientists have had difficulty exchanging genetic information between different strains, thereby complicating research efforts. Now Beatrice B. Magee, M.S., and Paul T. (Pete) Magee, Ph.D., are the first to produce mating strains of C. albicans. This discovery promises to accelerate research into the fungus and enable researchers to more quickly understand its biology and identify new drug targets. "There is no doubt that the identification of a sexual cycle will facilitate ongoing drug discovery programs and motivate pharmaceutical companies to begin new searches," says Dr. Magee.
Interest in C. albicans reproduction increased as scientists began to unravel the organism's genetic blueprint, a process that is nearing completion. Christina Hull and Alexander Johnson, Ph.D., researchers at the University of California in San Francisco, analyzed this blueprint and isolated potential genes that resembled those controlling mating in the common baker's yeast. When the Magees removed one of these genes from a C. albicans strain, they paired the organism with a mate that contained the missing gene. Once the two strains met, they fused just like their baker's yeast cousins. Hull and Johnson accomplished the same feat independently.
The finding has important implications beyond simplifying Candida research. "Scientists have shown that in another disease-causing fungus, Cryptococcus, one mating type is much more virulent than the other. If this is true for C. albicans it opens up a new approach to understanding how this microbe causes disease," explains Dr. Magee. The researchers expect their discovery to accelerate studies on how the fungus adapts to different environments and how it evades the body's defense mechanisms.
The Magee's studies also illustrate an important caveat of modern biomedical research, now rife with announcements of newly deciphered genetic blueprints. "Determining the sequence of the C. albicans genome was only one step in the process," says Dr. Dixon. "The Magees have worked for years to painstakingly analyze the biology and genetics of Candida. When the C. albicans DNA sequence revealed a few hints about the organism's reproductive processes, the Magees were poised to investigate these clues and take a giant stride towards understanding an important human pathogen. Without their strong history of basic research, it is unlikely that this discovery would have been made."
NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose, and treat illness such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
References:
BB Magee and PT Magee. Induction of mating in Candida albicans by construction of MTLa and MTLa strains. Science 2000;289:310-12.
CM Hull, RM Raisner, and AD Johnson. Evidence for mating of the "asexual" yeast Candida albicans in a mammalian host. Science 2000;289:307-309.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institute of Allergy and Infectious Diseases is a component of the National Institutes of Health, U.S. Department of Health and Human Services.
Journal
Science