Newswise — Researchers at the Technion - Israel Institute of Technology and the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, in collaboration with scientists in Israel and Spain, have discovered remarkable molecular properties of an antimicrobial peptide from the skin of the Australian toadlet. The discovery could inspire the development of novel synthetic drugs to combat bacterial infections
An antibacterial peptide that turns on and off
The researchers solved the 3D molecular structure of an antibacterial peptide named uperin 3.5, which is secreted on the skin of the Australian toadlet (Uperoleia mjobergii) as part of its immune system. They 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. This provides unique atomic-level evidence explaining a regulation mechanism of an antimicrobial peptide.
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 Technion structural biologist Prof. 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 in sterile conditions.
The study is a result of a collaboration between scientists at EMBL Hamburg and Technion, and groups in Israel and Spain. It is an example of EMBL’s approach to life science research in its next scientific Programme Molecules to Ecosystems. EMBL will integrate interdisciplinary approaches to understand the molecular basis of life in the context of environmental changes, and to provide translational potential to support advances in human and planetary health.
For more than a century, the Technion – Israel Institute of Technology has pioneered in science and technology education and delivered world-changing impact. Proudly a global university, the Technion has long leveraged boundary-crossing collaborations to advance breakthrough research and technologies. Now with a presence in three countries, the Technion will prepare the next generation of global innovators. Technion people, ideas and inventions make immeasurable contributions to the world, innovating in fields from cancer research and sustainable energy to quantum computing and computer science to do good around the world.
The American Technion Society supports visionary education and world-changing impact through the Technion – Israel Institute of Technology. Based in New York City, we represent thousands of US donors, alumni and stakeholders who invest in the Technion’s growth and innovation to advance critical research and technologies that serve the State of Israel and the global good. Over more than 75 years, our nationwide supporter network has funded new Technion scholarships, research, labs, and facilities that have helped deliver world-changing contributions and extend Technion education to campuses in three countries.