Using Substances Originally Developed to Treat Alzheimer’s, Scientists Could Neutralize Antibiotic-resistant Bacteria

September 13, 2019
Kevin Hattori

Biofilm formation

Left: Atomic structure of a segment from a protein that forms fibrils that structure the biofilm of E. coli and Salmonella bacteria. This structure is highly similar to that of the amyloid fibrils related to Alzheimer’s disease, and this structural similarity inspired the idea of harming the bacterial biofilm fibrils using substances developed to combat Alzheimer’s fibrils. Top (black and white): Micrographs taken with an electron microscope. The left image shows fibrils produced by bacterial proteins that serve to build the biofilm; the right image shows impairment in the formation of the fibrils as a result of adding the substance developed to combat Alzheimer fibrils (ANK6). Bottom (black and red): Three-dimensional images taken by a confocal laser scanning microscope after coloring the bacterial biofilm in fluorescent red. Left: High biofilm biomass. Right: Addition of ANK6 leads to a significant decrease in the amount of biofilm.

Researchers from the Technion Faculty of Biology may have found a way to make salmonella bacterial infections less aggressive by inhibiting the formation of biofilm, a layer of microorganisms that constitutes a serious medical and environmental problem because it protects bacteria and enables them to attach to tissues, medical devices, pipes and more. The discovery by Associate Professor Meytal Landau, doctoral student Nir Salinas, and the laboratory research team could lead to the development of innovative treatments that will inhibit the antibiotic resistance of virulent bacteria.

In 2017, Prof. Landau’s research team published an article in Science describing new discoveries about Staphylococcus aureus—an especially virulent bacterium that has become resistant to many types of antibiotics and that is responsible for a considerable number of infections in hospitals and in the community. The researchers discovered that this bacterium, which attacks the organism’s T-cells of the immune systems, does so in part by means of secreting certain fibrils. These toxic fibrils resemble amyloids, proteins associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s, but differ from them structurally. In an article published in Nature Communication in 2018, Nir Salinas and his colleagues on the research team revealed their discovery that proteins from the same family as the toxic fibrils produce exceptionally stable amyloid structures that can survive under extremely difficult conditions and protect the bacteria. Prof. Landau expressed the hope that these discoveries will lead to new treatments that will impair the fibrils and significantly diminish the aggressively virulent infections caused by Staphylococcus aureus.

Associate Professor Meytal Landau and Mr. Nir Salinas

In a recent study in PLoS Pathogens, the Technion researchers suggested that by interfering with amyloid fibrils produced by E. coli and Salmonella, bacteria often linked with contaminated water or food, they can hamper the bacteria’s defense mechanisms and their ability to attach to tissues and medical devices. This is accomplished by repurposing substances that have already undergone clinical trials for treating Alzheimer’s. The major advantage of this repurposing is that the approval process is much shorter and less expensive than in the case of a new compound.

The substances tested on Salmonella bacteria do not harm the bacteria directly. Instead, they damage the biofilm, the resilient layer that protects bacteria from substances that pose a danger to them, including antibiotic drugs. The researchers estimate that this approach of impairing the biofilm will reduce the risk of developing resistance compared to antibiotics that kill the bacterial and thereby induce defense mechanisms against the drug, making the bacteria more resilient and virulent.

The research examined the possibility of damaging Salmonella and E. coli bacteria found in contaminated food. Nevertheless, the researchers hope their discovery will also be effective in battling other bacteria, including Staphylococcus aureus. In his ongoing doctoral research, Mr. Salinas will focus on developing stable antibacterial substances and on examining small molecules that will interfere with the in-vitro assembly of amyloids in bacteria. He hopes these developments will accelerate the crucial battle against the development of virulent strains of antibiotic-resistant bacteria.

The research is being carried out in collaboration with the Institute for Complex Systems in Jülich and in Düsseldorf, Germany. The Technion Center for Structural Biology (TCSB), the Lorry Lokey Interdisciplinary Center for Life Sciences and Engineering, the Electron Microscopy Center, and the Center for Electron Microscopy of Soft Matter in the Russell Berrie Nanotechnology Institute (RBNI) also provided assistance for this project.

Associate Professor Landau joined the Technion faculty after completing post-doctoral studies at UCLA, where she specialized in X-ray micro-crystallography of amyloids associated with Alzheimer’s disease. In September 2012 she founded her laboratory in the Faculty of Biology at the Technion.

Mr. Nir Salinas completed his bachelor’s degree in molecular biochemistry in the Schulich Faculty of Chemistry at the Technion. Today he is following a direct program to a doctoral degree in the Faculty of Biology.

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