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Wisconsin scientists discover a master key to microbes' pathogenic lifestyles

For some microbes, the transformation from a benign lifestyle in the soil to that of a potentially deadly human pathogen is just a breath away.

Inhaled into the lungs of a mammal, spores from a class of six related soil molds found around the world encounter a new, warmer environment. And as soon as they do, they rapidly shift gears and assume the guise of pathogenic yeast, causing such serious and sometimes deadly afflictions as blastomycosis and histoplasmosis.

But how these usually bucolic fungi undergo such a transformation to become serious pathogens has always been a puzzle. Now, however, a team of scientists from the University of Wisconsin School of Medicine and Public Health reports the discovery of a master molecular sensor embedded in the spores of the fungi that triggers the transformation. The finding is reported in the April 28 edition of the journal Science.

The discovery could lead to new treatments, and possibly vaccines for the diseases caused by these Jekyll and Hyde microbes, says Bruce Klein, a UW-Madison professor of pediatrics, internal medicine and medical microbiology and immunology, and the senior author of the new study.

"These microbes have to undergo an extreme makeover to survive in a host," says Klein, an authority on fungal diseases. "The million dollar question is was what controls this change? "

Klein and colleagues Julie C. Nemecek and Marcel Wuthrich identified a molecular sensor that is conserved in these six related dimorphic fungi found worldwide. The sensor, says Klein, is like an antenna situated in the membrane of the fungi's spores. It senses temperature, and when a spore finds itself at a comfortable 37 degrees Celsius, the body temperature of a human or other animal, it kick starts a genetic program that transforms the fungi into pathogenic yeasts.

"This is a global regulator that sends signals down a molecular chain of command and governs a series of vital genetic programs,
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Source:University of Wisconsin-Madison


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