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A fungus called microsporidia that causes chronic diarrhea
in AIDS patients, organ transplant recipients, and travelers
has been identified as a member of the family of fungi that
have been discovered to reproduce sexually. A team at Duke
University Medical Center has proven that microsporidia are
true fungi and that this species most likely undergoes a form
of sexual reproduction during infection of humans and other
host animals.

The findings could help develop effective treatments against
these common global pathogens and may help explain their most
virulent attacks.

"Microsporidian infections are hard to treat because until
now we haven't known a lot about this common pathogen," says
Soo Chan Lee, PhD, lead author and a postdoctoral researcher in
the Duke Department of Molecular Genetics and Microbiology. "Up
to 50 percent of AIDS patients have microsporidial infections
and develop chronic diarrhea. These infections are also
detected in patients with traveler's diarrhea, and also in
children, organ transplant recipients, and the elderly."

Of the 1200 species of microsporidia, more than a dozen
infect humans. Their identity had been obscured because these
tiny fungi cannot live outside of an infected host cell and
they have a small number of genes which are rapidly
evolving.

The Duke scientists used two genetic studies to show that
microsporidia apparently evolved from sexual fungi and are
closely related to the zygomycete fungus in particular.

They found that microsporidia share 33 genes out of 2,000
with zygomycetes. which the microsporidia did not share with
other fungi. This genomic signature also shows that
microsporidia and zygomycetes likely shared a common ancestor
and are more distantly related to other known fungal
lineages.

In addition, these two types of fungi have the same
sex-locus genes -- and in the same order -- in their DNA. Other
genes involved in sexual reproduction are also present. The
findings suggest that microsporidia may have a genetically
controlled sexual cycle, and may be undergoing sexual
reproduction while they infect the host, Lee said.

Lee said the next step is to explore the sexual reproduction
of these species, which may cause more severe (more virulent)
infections because they use the host's cellular environment and
machinery as a safe haven in which to reproduce.

"These studies resolve the enigma of the evolutionary
origins and proper placement of this highly successful group of
pathogens, and provide better approaches to their experimental
study," said senior author Joseph Heitman, MD, PhD, director of
the Center for Microbial Pathogenesis and director of the Duke
University Program in Genetics and Genomics.

The team will pursue further studies with Duke genetic
researchers Raphael Valdivia, PhD, and Alejandro Aballay, PhD,
using cultured cells and C. elegans, a worm that researchers
recently found is a natural host for microsporidia. "Using this
roundworm may prove to be a useful way to study microsporidia
genetics in a living creature," Heitman said.

This work was published online in the Oct. 30 edition of
Current Biology, and was supported by grants from the National
Institute of Allergy and Infectious Diseases of the National
Institutes of Health, and by the Canadian Institutes for Health
Research.

Other authors on this study include Nicolas Corradi and
Patrick J. Keeling of the Canadian Institute for Advanced
Research, Department of Botany, University of British Columbia
- Vancouver; Edmond J. Byrnes III of the Duke Department of
Molecular Genetics and Microbiology; Santiago Torres-Martinez
of the Departamento de Genetica y Microbiologia, Facultad de
Biologia, Universidad de Murcia, Spain; and Fred S. Dietrich of
Duke Molecular Genetics and Microbiology and the Duke Institute
for Genome Sciences and Policy.