A Newly-Discovered Antibiotic Shows Why a Rich Biodiversity is Vital

Australian Western toadlet, Uperoleia mjobergii

Toadlet peptide transforms into a deadly weapon against bacteria | EMBL

Researchers at The European Molecular Biology Laboratory (EMBL), Heidelberg, Germany, together with colleagues from Technion - Israel Institute of Technology - have discovered a potential powerful new form of antibiotic - in the skin of an Australian Amphibian, the Western toadlet, Uperoleia mjobergii.

This discovery highlights the vital importance of maintaining a rich biodiversity on Earth because, if nothing else, we could be losing valuable sources of new medicines and antibiotics.

It consists of a polypeptide (a short chain of amino acids) that, when they come into contact with the cell membrane of a bacterium, change to become powerful bactericides. The researchers found that the peptide self-assembles into a unique fibrous structure, which via a sophisticated structural adaptation mechanism can change its form in the presence of bacteria to protect the toadlet from infections.

Distribution of Uperoleia mjobergii in Northwestern Australia

Map prepared by Jean-Marc Hero and Luke Shoo
School of Environmental & Applied Sciences, Griffith University, Australia

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The peptide uperin 3.5 is secreted by the Australian toadlet’s skin. When exposed to bacterial membranes, it rapidly changes its structure and transforms into a deadly antimicrobial weapon. The pictures were taken using a transmission electron microscope (TEM) in the Electron Microscopy Centers in the Technion Department of Materials Science and Engineering and in the Department of Chemical Engineering. The cross-α atomic structure was determined by data collected at the ESRF synchrotron.

Credit: Nir Salinas/Technion

As the EMBL new release explains:

The antibacterial fibrils on the toadlet’s skin have a structure that is reminiscent of amyloid fibrils, which are a hallmark of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Although amyloid fibrils have been considered pathogenic for decades, it has recently been discovered that certain amyloid fibrils can benefit the organisms that produce them, from human to microbes. For example, certain bacteria produce such fibrils to fight human immune cells.

The findings suggest that the antibacterial peptide secreted on the toadlet’s skin self-assembles into a “dormant” configuration in the form of highly stable amyloid fibrils, which scientists describe as a cross-β conformation. These fibrils serve as a reservoir of potential attacker molecules that can be activated when bacteria are present. Once the peptide encounters the bacterial membrane, it changes its molecular configuration to a less compact cross-α form, and transforms into a deadly weapon. “This is a sophisticated protective mechanism of the toadlet, induced by the attacking bacteria themselves,” says structural biologist Meytal Landau, the lead author of this study. “This is a unique example of an evolutionary design of switchable supramolecular structures to control activity.”

Potential for future medical applications

Antimicrobial peptides are found in all kingdoms of life, and thus are hypothesised to be commonly used as weapons in nature, occasionally effective in killing not only bacteria, but also cancer cells. Moreover, the unique amyloid-like properties of the toadlet’s antibacterial peptide, discovered in this study, shed light on potential physiological properties of amyloid fibrils associated with neurodegenerative and systemic disorders.

The researchers hope that their discovery will lead to medical and technological applications, e.g. development of synthetic antimicrobial peptides that would be activated only in the presence of bacteria. Synthetic peptides of this kind could also serve as a stable coating for medical devices or implants, or even in industrial equipment that requires sterile conditions.

The teams findings were published recently in PNAS, unusually for PNAS behind an expensive paywall.

As mentioned above, this discovery highlights the importance of maintaining Earth's biodiversity since there is no way to predict where useful chemicals like this potential powerful antibiotic are going to be found. In this instance, the discovery could also shed light of the mechanism behind neurodegenerative conditions such as Alzheimer’s.

As can be seen from the distribution map, this toadlet has a limited distribution and so is susceptible to local environment destruction and climate change. It was assessed in 2004 as 'Least concern' for the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. It is distributed in a remote part of Australia with a low population and little environmental disturbance. This may not always be so, of course, and is certainly not so for very many other species worldwide.

The Worldwide Fund for Nature (WWF) has this to say about the rate at which we are exterminating different species.

Just to illustrate the degree of biodiversity loss we're facing, let’s take you through one scientific analysis...

• The rapid loss of species we are seeing today is estimated by experts to be between 1,000 and 10,000 times higher than the natural extinction rate.*
• These experts calculate that between 0.01 and 0.1% of all species will become extinct each year.
• If the low estimate of the number of species out there is true - i.e. that there are around 2 million different species on our planet** - then that means between 200 and 2,000 extinctions occur every year.
• But if the upper estimate of species numbers is true - that there are 100 million different species co-existing with us on our planet - then between 10,000 and 100,000 species are becoming extinct each year.

*Experts actually call this natural extinction rate the background extinction rate. This simply means the rate of species extinctions that would occur if we humans were not around.

** Between 1.4 and 1.8 million species have already been scientifically identified.

Earth's animals and plants are a resource that we simply can't afford to squander because, as they say, there is no Planet B.

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