Scientists discover a master key to microbes' pathogenic lifestyles

How fungi undergoes the transformation into serious pathogens has always been a puzzle to scientists, now however, a team of scientists from the University of Wisconsin-Madison School of Medicine and Public Health has discovered a master molecular sensor embedded in the spores of the fungi that triggers the transformation.

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 paediatrics, internal medicine and medical microbiology and immunology, and the senior author of the 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.

Klein explains the sensor as being 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°C, 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," Klein says. "It leads to changes in the organism's metabolism, cell shape, cell wall composition, and changes in virulence gene expressions."

These changes, according to Klein, are really a survival program for the microbe, conferring resistance to the host's immune responses.

The diseases caused by the fungi can be especially serious for immune compromised individuals, and some human populations seem to be more at risk for acquiring the infections.

"All of these organisms exhibit this property of latency," says Klein. "They can remain dormant until immune defences are lowered. It's a significant medical problem in endemic regions."

The discovery of the switch that governs dimorphism and virulence in this prevalent class of fungi provides a target for new therapeutic agents and might even help underpin a vaccine able to thwart infection entirely, according to Klein.

"This could lead to therapeutics, better treatment for this class of diseases," Klein explains. "And with this finding, vaccines might now be possible. That's a strategy with promise."

The discovery of a master switch in related but diverse and geographically widespread class of fungi is an indication that it was inherited from a common ancestor deep in evolutionary history.

"It is a story of how organisms are challenged in a new environment," says Klein. "They have to make themselves over so they can survive."

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