Scientists Discover a Master Key to Microbes' Pathogenic Lifestyles Libraries

[Guest guest]

Source: University of Wisconsin-Madison Released: Mon 24-Apr-

2006, 18:20 ET

Embargo expired: Thu 27-Apr-2006, 14:00 ET

http://www.newswise.com/articles/view/519905/

Scientists Discover a Master Key to Microbes' Pathogenic Lifestyles

Libraries

Medical News Keywords

MICROBES, PATHOGENIC, SPORES, BLASTOMYCOSIS, HISTOPLASMOSIS

Contact Information

Available for logged-in reporters only

Description

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 pathogenic fungi that

triggers the transformation from benign to potentially deadly.

Newswise — 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 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, "

Klein explains. " 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. For example, U.S.

soldiers who train in the American Southwest tend to be susceptible

to coccidiomycosis because the organism that causes it is endemic to

the region. One in three of those who train there acquire the

disease, considered to be the second most common fungal infection in

the United States. Of those infected, 25 percent contract pneumonia.

Histoplasmosis, a disease caused by the fungus Histoplasma

capsulatum, infects as much as 80 percent of the population where

the organism is endemic, including much of the eastern and central

United States. It is also widespread in South America and Africa. In

most instances, the infection prompts only mild symptoms. Untreated,

however, it can be fatal. What's more, the microbe can lay dormant

in an infected host for years.

" All of these organisms exhibit this property of latency, " says

Klein. " They can remain dormant until immune defenses 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 acquired from a common ancestor deep in evolutionary history.

The feature is a common mechanism used by the different organisms to

adapt to a new environment: the lungs of animals.

" 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. "

The Wisconsin study was funded by grants from the National

Institutes of Health.

[Guest guest]

WOW, great find KC, thanks

>

> Source: University of Wisconsin-Madison Released: Mon 24-Apr-

> 2006, 18:20 ET

> Embargo expired: Thu 27-Apr-2006, 14:00 ET

>

>

> http://www.newswise.com/articles/view/519905/

>

> Scientists Discover a Master Key to Microbes' Pathogenic Lifestyles

> Libraries

> Medical News Keywords

> MICROBES, PATHOGENIC, SPORES, BLASTOMYCOSIS, HISTOPLASMOSIS

> Contact Information

>

> Available for logged-in reporters only

> Description

>

> 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 pathogenic fungi that

> triggers the transformation from benign to potentially deadly.

>

>

>

> Newswise — 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 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, "

> Klein explains. " 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. For example, U.S.

> soldiers who train in the American Southwest tend to be susceptible

> to coccidiomycosis because the organism that causes it is endemic

to

> the region. One in three of those who train there acquire the

> disease, considered to be the second most common fungal infection

in

> the United States. Of those infected, 25 percent contract pneumonia.

>

> Histoplasmosis, a disease caused by the fungus Histoplasma

> capsulatum, infects as much as 80 percent of the population where

> the organism is endemic, including much of the eastern and central

> United States. It is also widespread in South America and Africa.

In

> most instances, the infection prompts only mild symptoms.

Untreated,

> however, it can be fatal. What's more, the microbe can lay dormant

> in an infected host for years.

>

> " All of these organisms exhibit this property of latency, " says

> Klein. " They can remain dormant until immune defenses 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 acquired from a common ancestor deep in evolutionary history.

> The feature is a common mechanism used by the different organisms

to

> adapt to a new environment: the lungs of animals.

> " 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. "

>

> The Wisconsin study was funded by grants from the National

> Institutes of Health.

>