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Chemists around the world are involved in a race against time
to find a solution to the growing problem of bacteria becoming
resistant to antibiotics. It's a major threat to the health of
the global population, which had long assumed that antibiotics
would always be available to cure bacterial illness.
The scientific community hopes to be able to develop a new range
of antibiotics to replace those that are increasingly losing
their ability to work against infections like Tuberculosis (TB).
A research team led by Markus Aebi, Professor of Mycology at ETH
Zurich (the Swiss Federal Institute of Technology in Zurich),
believe they may have found the answer.
They discovered copsin in the common inky cap mushroom
Coprinopsis cinerea that grows on manure, while researching how
the fungus and various bacteria affected each other's growth.
According to lead researcher, post-doc Andreas Essig, horse
manure's rich substrate is key.
"Horse dung is a very rich substrate that harbours a diversity
of micro-organisms, including fungi and bacteria," said Essig.
"Now these micro-organisms are in a constant competition for
nutrients and space and it's therefore very likely to find
potent antibiotics in such an environment, which are used by the
different organisms to inhibit the growth of the competitors."
Essig and his colleagues from ETH Zurich and the University of
Bonn cultivated the fungus in a laboratory, along with several
different types of bacteria, and found that C. cinerea killed
certain bacteria. Further research demonstrated that the copsin
produced by the mushroom was responsible for this antibiotic
effect.
"Now copsin kills bacteria by binding to an essential cell wall
building block," said Essig. "The cell wall you can consider
like the achilles heel of bacteria, so when you disrupt the cell
wall synthesis bacteria usually dies rapidly. The binding
pattern of copsin on this building block is very unique and
therefore copsin is active against bacteria resistant to
conventional antibiotics."
Copsin is a protein, whereas traditional antibiotics are often
non-protein organic compounds. It belongs to the group of
defensins, a class of small proteins produced by numerous to
counter disease-causing micro-organisms. In fact, the human body
produces defensins in the skin and mucous membranes to protect
itself against infections.
To yield larger amounts of the antibiotic, copsin is produced in
liquid culture via a methylotrophic yeast called Pichia
pastoris. Speaking in the ETH Zurich laboratory while producing
copsin, senior scientist PaulI Kallio said: "We are growing
Pichia pastoris, which is a methylotrophic yeast and in this
yeast we are producing copsin, so this is a long process, and
that is why we are using bioreactors which then provides
controlled and sterile environment for copsin production."
Kallio says the cultivation process takes five days, before
cells can be harvested and copsin extracted.
Essig says copsin's inherent stability is crucial to its
potential use and that it could be useful in the food industry,
because it kills pathogens such as Listeria, a type of bacteria
that can cause severe food poisoning. "Copsin is an
exceptionally stable protein, so you can for example boil it at
100 degrees, you can put it in strong acid for hours," he said.
"You can also treat it with very aggressive enzymes and it
remains completely active. This feature allows us, for example,
also to go into applications in food industry, food
preservation, productions where strong acids in high
temperatures are very common."
Aebi says it is not certain whether copsin could be used in an
antibiotic, but that even if it cannot it remains important
research. He is intrigued by what he calls the fundamental
question of how fungi have used defensins and other naturally
antibiotic substances for millions of years to protect
themselves against bacteria, while antibiotics used in medicine
by humans have developed resistance in just 70 years.
The team has registered copsin for patent approval.
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