Researchers at the Faculty of Biology at the Technion have deciphered a mechanism that protects the Australian toad from hostile bacteria
Researchers at the Faculty of Biology at the Technion deciphered the three-dimensional structure, at the atomic level, of an antibacterial peptide called ufrin 3.5, which is secreted on the skin of an Australian toad as part of its immune system, and discovered that it creates, by self-organization, a unique fibrous structure. Beyond that, they discovered that the fiber The special feature is a sophisticated structural adjustment mechanism that provides the toad with active protection in the presence of the bacteria attacking it. Understanding the structure of this peptide and its mechanism of action may help in the development of effective, stable antibacterial drugs that are activated only in the presence of bacteria. The research published in the journal PNAS was led by Prof. Mittal Landau, Dr. Nir Salinas and Dr. Einav Taib-Fligelman while cooperating with their colleagues in Israel and Spain.
The structure of the antibacterial fiber from the toad resembles amyloid fibers known to the medical world in the context of neurodegenerative diseases such as Alzheimer's and Parkinson's. In these diseases, the amyloid fibers accumulate in the brain and cause damage to brain functions gradually. However, in recent years it has become clear that certain amyloid fibers can play different roles for the benefit of the organism that produces them, starting with humans and ending with microbes. For example, some bacteria produce such fibers as a weapon that they use to damage the cells of the host organism.
Prof. Landau's research group is responsible for one of the breakthroughs in this regard - First deciphering of the three-dimensional structure of bacterial amyloid fibrils. Prof. Landau published the new structure, called cross-α, in the journal Science in 2017. In the same article, the amyloid fiber in the Staphylococcus aureus bacterium was presented and its function as a weapon ("poisonous arrow") that increases the bacterium's violence against the immune system was described.
The mechanism they currently propose describes the antibacterial peptide secreted on the skin of the toad in a "dormant" configuration that is not active against bacteria, in which the peptide molecules are organized into a cross-β type amyloid fiber, Characterized by high stability and therefore well preserved. These fibers constitute a "reservoir" of potential attack molecules that arise when needed. When exposed to bacteria, those peptides come into contact with the fat molecules of the bacteria's cell membranes, as a result a structural change occurs and the fiber turns into a cross-α configuration - the same configuration that the research group discovered in 2017. This change transforms the fiber For a deadly weapon that destroys the bacteria that attack the toad's skin. "This is a sophisticated defense mechanism of the toad, which is activated by the very bacteria that attack it" - says Prof. Landau. "This is a unique example of an evolutionary design of a change in supramolecular structure to control activity."
Since antimicrobial peptides are present in all kingdoms of the animal world, there is a basis for assuming that they were created at early stages in evolution, and are a common weapon in nature. This research contributes greatly to the understanding of innovative mechanisms of action of antimicrobial peptides, which are involved not only in inhibiting bacterial infections but also in killing cancer cells. Moreover, this discovery contributes to a deeper understanding of the physiological role and properties of the amyloid fibers associated with neurodegenerative diseases.
The researchers hope that the scientific discovery will lead to medical and technological applications, partly in the context of the complex fight against the development of bacterial resistance to antibiotics. In their estimation, it is possible that the toad peptide's sophisticated modification mechanism will provide inspiration for development Artificial peptides which will be more effective and more stable than existing treatments in eliminating harmful and dangerous bacterial infections, and for a stable coating of medical devices, implants, and industrial equipment, which will be activated only in the case of the presence of bacteria.
Prof. Landau is a faculty member in the Faculty of Biology and Food and a member of EMBL – European Molecular Biology Laboratory in Hamburg, Germany.
