Amyloids are notorious mainly because of their involvement in neurodegenerative diseases of the nervous system such as Alzheimer's and Parkinson's, both of which are characterized by the accumulation of clumps of these precipitates in brain cells. In contrast to the amyloids related to these diseases, microorganisms, such as bacteria, produce functional amyloids that are involved in many activities that benefit the organism producing it.

Recently, investigators hypothesized that these functional amyloids take part in the disease mechanism of the violent Staphylococcus aureus bacterium, which causes severe infections. The bacterium secretes amyloid–forming proteins into the bloodstream that kill blood and immune cells. One of these proteins, the highly toxic 3alphaPSM, is related to the infectious potential of Staphylococcus bacteria. Led by Associate Professor Meytal Landau, researchers from the Faculty of Biology at the Technion unraveled a key step in this process and discovered a surprising finding regarding these bacterial amyloids.

As with any protein, 3alphaPSM also consists of a chain of amino acids arranged like beads on a string. The function of the protein, among other things, is determined by the way this chain is organized in its three–dimensional structure. Two of the most common forms of structural proteins include a helical shape, where the chain is organized as a spiral, and a flat structure, where the chain is organized as a sheet.

Fibrils of amyloids involved in neurodegenerative diseases are constructed from flat sheets. However, when PhD student Einav Tayeb–Fligelman and Dr. Orly Tabachnikov used X–ray crystallography to examine in detail the structure of this bacterial protein, they were surprised to find that the fibers actually consisted of helical proteins.

To understand the relationship between the amyloid protein structure and its toxicity, the researchers created mutations in the DNA of bacteria, resulting in the replacement of some amino acids in the protein chain, so that fibers cannot be formed. Testing these mutated proteins on cultures of immune cells, revealed that most of their toxicity was lost. However, when the fibers were formed, the protein killed these immune cells. The researchers concluded that the helical structure is important for creating the fibers, and thus for the toxicity of the bacteria. However if the spiral structure exists alone without the construction of the protein fibers, toxicity was still significantly reduced.

To prove that this wasn’t a special case of toxicity against the cells of the immune system, the researchers repeated the experiment with another type of human cell; a model system used in many other studies, using kidney cells of a fetus, and achieved similar results. In an article published in the journal Science, it was stated that this activity is not specific to particular cells, but rather a general mechanism that allows bacteria to attack cells with the help of these functional amyloids.

“What prompted us to investigate the atomic structure of 3alphaPSM was the desire to explore amyloid functioning in bacteria and to see how similar their structure is to the amyloid associated with Alzheimer's disease,” said Landau for the Davidson Institute website. “Although both types of amyloids form fibers, after we determined the structure of the bacterial protein at the atomic level, we found, to our surprise, that despite their general similarity to disease–related amyloids, the bacterial amyloid protein creates a fibrous structure that was not previously known.”

The next step for Landau and her colleagues is to find ways to use this discovery as the basis for searching for new antibiotics.