Nearly all organisms need iron to survive, even mould

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A Grab for Iron - Breakthrough for Innsbruck Scientists

http://www.innovations-report.com/html/reports/life_sciences/report-

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Nearly all organisms need iron to survive, even mould. For people

with

a weakened immune system such fungi pose a deadly threat. Scientists

from Innsbruck (Austria) have now been able to genetically block the

iron metabolism of Aspergillus fumigatus mould and thus render it

harmless to humans. This discovery opens up completely new paths for

developing drugs against fungal infections.

The Aspergillus fumigatus mould is commonly found in compost, green

bins, potting compost and on wallpaper. For people with a weakened

immune system it can become dangerous, attacking organs like lung,

stomach, intestine and the nervous system. Because it is difficult

to

diagnose and treat, such a mould infection (aspergillosis) becomes

life-threatening for patients whose immune system has been affected

by

chemotherapy, HIV infection or an organ transplant. Bacteria can be

overcome quite effectively with antibiotics, but there are as yet

hardly any effective drugs against mould, which accounts for the

fact

that 80 percent of affected patients do not survive such an

infection.

Fighting mould

Now, for the first time, a working group headed by Hubertus Haas and

Markus Schrettl of the Department for Molecular Biology of Innsbruck

Medical University has managed to genetically block the iron

metabolism

of the mould. In a recent article in the acclaimed scientific

Journal

of Experimental Medicine they proved that the siderophore system is

essential for the virulence of Aspergillus fumigatus. The mould uses

the so-called siderophores for the reception of vital iron.

These low-molecular-weight peptides can bind iron and are sent out

by

the cells to absorb iron as well as being used inside the cell to

store

it. If this siderophore system is systematically disrupted, the

fungus

loses its essential iron supply and dies. In animal modelling this

has

been proven successfully. Being able to understand this mechanism

offers very promising perspectives for the development of new

therapies

against fungal infections. Of particular advantage is the fact that

humans do not have a comparable system, which bodes well for

potential

inhibitors having few side-effects.

" Gaining detailed insights into the siderophore metabolism enables

us

to investigate the system as a potential handle for combating

aspergillosis and other fungal infections, " Hubertus Haas explained

the

impact of this breakthrough. " So far we have been able to identify

at

least 30 genes with gene products involved in this system. At the

moment we are carrying out microarray-profiling, which should

uncover

additional factors, " Haas continued.

Basic research and application potential

The working group from Innsbruck has been exploring the iron

metabolism

of mould since 1998, supported by research funds from the Austrian

Science Foundation (FWF) and the Austrian National Bank (ÖNB). As

the

new approaches for antifungal therapies show, there is a wealth of

application potential in such basic molecular-biology research into

identifying and characterizing the siderophore system. A novel

screening process for antifungal substances – for which a patent is

pending – recently won the Life Science Business Award of the Center

for Academic Spin-offs Tyrol (CAST).

More information: www.i-med.ac.at

www.jem.org