Equine ordure: NMR reveals fungal antibiotic

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  • Published: Dec 1, 2014
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Equine ordure: NMR reveals fungal antibiotic

A stable antibiotic protein

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)

NMR spectroscopy reveals the structure of an antibiotic protein, copsin, from a surprising source: the grey shag fungus that grows on horse dung. The stable antibiotic has the same ultimate effect on bacteria as small molecule compounds but offers an entirely different biochemistry that might be exploited in drugs to defeat antibiotic resistance.

Microbiologists and molecular biologists at the Institute of Microbiology at ETH Zurich, Switzerland and colleagues at the University of Bonn, Germany, named the newly discovery antibiotic copsin. Mycologist Markus Aebi and colleagues unearthed copsin from the common inky cap mushroom Coprinopsis cinerea, which grows on horse manure. The original aim of the work was to discovery how this fungus interacts with bacteria and what effect they each have on the other's growth. The laboratory work involved cultivating the fungus it having been inoculated with several different types of bacteria. They quickly discovered that C. cinerea can kill certain bacteria and that copsin was the agent of bactericide.

Defensive moves

Copsin is one of a group of proteins known as defensins, a class of small proteins made by many organisms, including humans, to combat invading pathogenic microbes. Defensins are often present on our skin and in our mucous membranes. "Whether copsin will one day be used as an antibiotic in medicine remains to be seen," says Aebi. "This is by no means certain, but it cannot be ruled out either," he says. Critically, the pharmaceutical industry tends to market small molecule drugs for their ease of control and production although there are peptide and protein products out there. Moreover, in the age of failing antibiotics, a complicated mode of action might turn out to be the optimal alternative.

Aebi is nevertheless interested in the fundamental science pertaining to the millions of years of fungal evolution, the emergence of defensins and other natural antibiotic substances. Why does this biochemical strategy work for fungi but bacteria evolved resistance almost as soon as the first antibiotic was prescribed for a human 70 years ago. "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. Moreover, it holds the promise of unravelling their secret and exploiting it in medicine.

On the hoof

The team has applied for a patent for copsin and postdoctoral researcher Andreas Essig, lead author on the paper, is currently looking at possible applications. "Copsin is an exceptionally stable protein," explains Essig. Proteins are generally susceptible to protein-degrading enzymes and high temperatures but copsin manages to hold itself together even at boiling water temperature for several hours, perhaps due to its extremely compact three-dimensional structure, as revealed by nuclear magnetic resonance (NMR) spectroscopy.

The ETH team has also found that copsin binds to lipid II, an essential building block for the cell wall of bacteria. "Building the cell wall is the Achilles' heel of bacteria," Essig explains. Copsin blocking the building of new bacterial cell wall means the bacterium cannot multiply. If copsin does not find use as a medical antibiotic for treating bacterial infections it might nevertheless find application in the food industry as an additive to kill pathogens, such as listeria, salmonella, campylobacter, E coli O157 and others that cause severe and sometimes lethal forms of food poisoning. The antibacterial protein would presumably survive boiling and so remain active in food that was not eaten immediately.

Related Links

J Biol Chem 2014, online: "Copsin, a novel peptide-based fungal antibiotic interfering with the peptidoglycan synthesis"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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