Fungus Protein That Attacks Pathogenic Fungi - Fungicide From Penicillium

A fungus protein that attacks pathogenic fungi is the focal point of a
project recently launched by the Austrian Science Fund FWF. As well as
examining the structure of the protein, the project will also closely
analyse the physiological changes that it causes in the cells of pathogenic
fungi. Combined with findings from an earlier project, the new data could
form the basis for the development of an effective treatment of certain
fungal infections.



PAF, NAF, AFP and ANAPF make up the new class of proteins that can restrict
the growth of certain hyphomycetes - and which are themselves a product of
this type of fungi. Although one can only speculate about their biological
function, they offer enormous potential for the development of an effective
treatment of fungal infections in plants, animals and people. Prof.
Florentine Marx from the Biocenter of Innsbruck Medical University has been
working on one of these proteins - PAF, or Penicillium Antifungal Protein -
for several years. The Austrian Science Fund FWF has been providing ongoing
support for her work since 2001 and is now continuing this support.



A SHINING EXAMPLE


During the new project, Prof. Marx's team will be using a modified strain of
the PAF-sensitive fungus Aspergillus nidulans as a model organism. As the
concentration of calcium ions in the cells of this fungus increases, it
produces light emissions that can be measured. Prof. Marx explains the
significance of calcium in this context: "Calcium acts as a universal signal
that controls certain processes in the cells. A gradient of the ion controls
growth in the filamentous fungus cells, or hyphae. The exposure to small
amounts of PAF in the hyphae of A. nidulans leads to a significant increase
in the concentration of calcium and a major change in growth patterns.
During this new project, we will be investigating whether these developments
are linked and, if so, how."


Another aim of the project is to identify mutated forms of A. nidulans that
are resistant to PAF. By analysing these mutated fungi, the project team
will characterise any molecular targets that must be responsible for
sensitivity to PAF in the case of wild types. During a subsequent stage in
the project, the team will produce modified forms of PAF and analyse the
effects they produce in A. nidulans. By also analysing the structure of the
modified forms of the protein, the project team will be able to draw
conclusions about which structural motifs of PAF are responsible for its
effect in the target organism. On a molecular genetic level, Prof. Marx's
team will identify the genes that are regulated by PAF.



RADICAL RESPONSE


The previous project has already enabled Prof. Marx and her team to clarify
key questions regarding the effect of PAF. Prof. Marx explains: "A high
dosage of PAF provokes apoptosis - programmed cell death - in the hyphae of
sensitive fungi such as A. nidulans. A dramatic succession of events that
take place on a cellular level are primarily responsible for this. These
include an increase in the electrical potential of the cell membrane, the
activation of potassium channels and a rise in the concentration of
cell-damaging free radicals. This latter event seems to be a key causative
factor of cell death."


Prof. Marx's project meets the urgent need for the characterisation of new,
effective fungicides. This need has increased dramatically over recent years
as a result of the growing resistance to existing treatments exhibited by
pathogenic fungi and, more significantly, due to major improvements in
intensive care medicine. Such medical advances often weaken the immune
system of patients, which enables fungal infections to take hold that would
normally be easily fought off by the body's defences. By continuing to
support the successful work of Prof. Marx and her team, the FWF is helping
to lay the foundations for finding a solution to this medical problem.



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