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 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
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
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."
BB Magee and PT Magee. Induction of mating in Candida
albicans by construction of MTLa and MTLa strains. Science
CM Hull, RM Raisner, and AD Johnson. Evidence for mating of
the "asexual" yeast Candida albicans in a mammalian host.