Deadly weapon: frog peptide

An unassuming Australian amphibian may inspire novel synthetic drugs to combat bacterial infections, according to European researchers.

In a paper published in the journal PNAS, the team – led by the Technion–Israel Institute of Technology and the European Molecular Biology Laboratory (EMBL) – discovered intriguing molecular properties of an antimicrobial peptide that is secreted on the skin of Mjoberg’s toadlet (Uperoleia mjobergi).

This tiny critter, the size of a dollar coin, is native to the Kimberley region in WA. It received its cute moniker because it looks “toad-like”, despite having no relation to true toads – it’s actually a frog.

Frog expert Jodi Rowley, curator of amphibian and reptile conservation biology at the Australian Museum in Sydney, explains that many of Australia’s 240 native frog species secrete a cocktail of chemical compounds on their skin. These protect the frogs from pathogens like bacteria and fungi – not to mention predators.

“We are increasingly realising that us humans can also benefit from understanding and potentially synthesising these peptides for our own use, particularly in the medical field,” says Rowley, who was not involved in the study.

“Many of these peptides – such as that demonstrated in this new research – act in strange or unexpected ways, and may inspire new tools in our fight against aggressive or even antibiotic resistant infections.”

In the new study, the team solved the 3D molecular structure of the peptide secreted by Mjober’s toadlet and found that it self-assembles into a unique fibrous structure.

This structure appears to serve as a dormant reserve of “attacker” molecules: when faced with different bacteria, it can tailor its molecular configuration to transform into a deadly weapon, thus protecting the toadlet from infection.

“This is a sophisticated protective mechanism of the toadlet, induced by the attacking bacteria themselves,” says structural biologist Meytal Landau, lead author from the Technion–Israel Institute of Technology. “This is a unique example of an evolutionary design of switchable supramolecular structures to control activity.”

Interestingly, the fibrous structure is reminiscent of amyloid fibrils – aggregations of proteins that are a hallmark of neurodegenerative diseases like Alzheimer’s and Parkinson’s. So this research may add to our understanding of the physiological properties of these fibrils.

For many decades, amyloid fibrils were thought to be pathogenic (that is, cause disease), but recently researchers have realised that they can also benefit the organisms that produce them.

The researchers therefore hope that their discovery of the toadlet’s antibacterial peptides will lead to medical and technological applications, including developing drugs based on synthetic peptides that only activate when in the presence of certain bacteria. In addition, such peptides could be used as a stable coating for medical devices, implants, or even industrial equipment.

Rowley says this new research is also an important addition to our understanding of the natural world.

“It highlights just how much we have to learn – and gain – from plants and animals,” she says.

“All over the world, frogs are facing enormous threats, and hundreds of species of frog are already been driven to extinction. The fact that frogs may hold the clue to saving our own lives is yet another reason to halt the loss of frog species, and the loss of biodiversity more generally.”