The highly pathogenic Staphylococcus aureus bacteria is one of the top five causes of hospital-acquired infections. From 1999 through 2005 in the US alone the estimated number of S. aureus related hospitalizations increased 62%, from 294,570 to 477,927.
Publishing in Science, Prof. Meytal Landau of the Faculty of Biology has unveiled a radical insight into how the bacteria works within the body. The revelation is found in unique amyloid fibrils, through which the pathogenic Staphylococcus aureus bacterium attacks the human cells and immune system. The research could advance the discovery of antibiotics with new strategies to disable key bacterial toxins.
Amyloids are proteins in cells that are known in association with neuro-degenerative diseases such as Alzheimer’s and Parkinson’s. The amyloids form a web of protein fibrils characterized by an orderly and extremely stable structure. This stability enables them to withstand extreme conditions in which ordinary proteins die.
One of the best-known examples of this is the 1986 “Mad Cow” disease outbreak in England. According to Prof. Landau, “This disease surprised the scientific community because its cause was not a virus, nor a bacterium, but a protein called Prion, possessing an amyloid-like structure. It then became clear that a protein can be transmissible, and due to its stability, it infected human beings who consumed the contaminated beef – meaning, the protein did not break down in the stages of meat processing, cooking and digestion.”
Landau estimates that the discovery will lead to the development of antibiotics with a new action mechanism. “From the very first moment, it was clear to us that what we had was a paradigm shift,” says Landau. Such drugs will inhibit the amyloid formation but not kill the bacteria, thus reducing the risk of bacterial resistance. “Resistance to antibiotics develops in bacteria due to evolutionary pressure. If we reduce the pressure on the bacterium and don’t kill it but rather prevent its pathogenic aspects, the resistance may not rush to develop.”
The research was conducted by members of the Landau lab, including Einav Tayeb-Fligelman, Orly Tabachnikov, Asher Moshe and Orit Goldshmidt- Tran, with the assistance of Michael Sawaya from the University of California Los Angeles (UCLA), and of Nicolas Coquelle and Jacques-Philippe Colletier from Université Grenoble, France.