ETH Zurich, Fabio Bergamin, 7 Nov 2014
Researchers
from the Institute of Microbiology at ETH Zurich have discovered a new protein
with antibiotic properties in a mushroom that grows on horse dung. Researchers
are now exploring the various potential applications.
 |
| The scientists isolated the new active compound from the grey shag that grows on horse dung. (Photo: Andreas Gminder / mushroomobserver.org / CC BY-NC-SA 3) |
Microbiologists
and molecular biologists at ETH Zurich and the University of Bonn have
discovered a new agent in fungi that kills bacteria. The substance, known as
copsin, has the same effect as traditional antibiotics, but belongs to a
different class of biochemical substances. Copsin is a protein, whereas
traditional antibiotics are often non-protein organic compounds.
The
researchers led by Markus Aebi, Professor of Mycology, discovered the substance
in the common inky cap mushroom Coprinopsis cinerea that grows on horse dung.
When they began their research, the scientists were interested in understanding
how this fungus and various bacteria affect each other's growth. This involved
cultivating the fungus in a laboratory along with several different types of
bacteria. It was found that C. cinerea is able to kill certain bacteria.
Further research demonstrated that the copsin produced by the mushroom is
responsible for this antibiotic effect.
Copsin
belongs to the group of defensins, a class of small proteins produced by many
organisms to combat microorganisms that cause disease. The human body also
produces defensins to protect itself against infections. They have been found,
for example, on the skin and in the mucous membranes.
A question
for basic research
For Aebi,
the main focus of this research project was not primarily on applications for
the new substance. “Whether copsin will one day be used as an antibiotic in
medicine remains to be seen. This is by no means certain, but it cannot be
ruled out either,” he says.
The ETH
professor is much more intrigued by fundamental questions, such as how fungi
have used defensins and other naturally antibiotic substances for millions of
years to protect themselves against bacteria. Why does this work for fungi
while humans have been using antibiotics in medicine for just 70 years with
many of them already becoming useless due to resistance? “Fungi have internal
instructions on how to use these substances without resulting in selection of
resistant bacteria. How to decode these instructions is an intriguing problem
for basic research,” explains Aebi.
An
extremely stable protein
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| The three-dimensional structure studied by ETH researchers exhibits the compact form of copsin. (Source: Essig A et al. JBC 2014) |
Andreas
Essig, a postdoc in Aebi's group and lead author of the study, is currently
exploring potential applications for copsin that has been registered for patent
approval. It was the biochemical properties of the substance that led the
scientist to do so. “Copsin is an exceptionally stable protein,” says Essig.
Proteins are generally susceptible to protein-degrading enzymes and high
temperatures. Copsin is an exception because it also remains stable when heated
to a temperature of 100 degrees Celsius for several hours or when subjected to
protein-degrading enzymes. The researchers believe that the protein has these
properties because of its extremely compact three-dimensional structure, as NMR
spectroscopy has shown.
The ETH
researchers were also able to unravel the exact mechanism of action,
discovering that copsin can bind to lipid II, an essential building block for
the cell wall of bacteria. “Building the cell wall is the Achilles heel of
bacteria,” explains Essig. If copsin binds to lipid II, the bacteria die
because they are unable to build new cell wall.
In addition
to being used as an antibiotic in medicine, it may also be possible to use
copsin in the food industry as well. This is because copsin kills many
pathogens including Listeria, a type of bacteria that can cause severe food
poisoning and is therefore feared, especially in the production of non-heat
treated foodstuffs such as raw milk cheeses and dried meats.
Literature
reference
Essig A,
Hofmann D, Münch D, Gayathri S, Künzler M, Kallio PT, Sahl HG, Wider G,
Schneider T, Aebi M: Copsin, a novel peptide-based fungal antibiotic
interfering with the peptidoglycan synthesis. Journal of Biological Chemistry,
online publication 23 October 2014, doi: 10.1074/jbc.M114.599878
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