The University of Bern molecular biologists have discovered a mechanism that will enable a deadly toxin to penetrate and destroy human cells. This could serve as a rational framework for the design and development of some new anti-toxin drugs. Pathogenic bacteria produce a variety of toxins in order to attack their hosts. Some of the toxins have been classed as potential bioterrorism weapons, as a particularly efficient and deadly type of toxin that punches holes in the membrane of host cells and kills them. These are pore-forming toxins and found in a large number of bacteria.
The bacterium called aeromonas hydrophila produces a pore-forming toxin called autolysin. By killing out the cells that line the gut of their host or those that are exposed at the surface of an open wound, aerolysin helps the bacterium to feed on the released cell content and penetrate deeper in the human body. With the gut cell death the patient will suffer from severe diarrhea. Sepsis and deep wound infections can be caused in humans from A. hydrophila.
Aerolysin and the majority of pore forming toxins are secreted by the bacterium as fully water-soluble proteins, which assemble and insert into the host cell membrane to become genuine transmembrane proteins.
An international group of biologists led by the University of Bern, and participation of the EPFL, have obtained the atomic structure of aerolysin prior, during and after membrane insertion by using state of the art electron microscopy technology and several designed aerolysin mutants. This study is being published in Nature Communications.
Benoit Zuber from the institute of Anatomy at the University of Bern says that aerolysin is a toxin with extreme stability that is due to its novel protein core design termed double concentric beta-barrel.
Aerolysin can actually transform itself like a quick-change artist and understanding these changes should be very useful to design new and more potent drugs against diseases resulting from Aeromonas infection.
The pioneering nanotechnology research from other groups has shown that aerolysin could be used as a very powerful tool to sequence DNA. Direct electron detectors, a new generation of digital cameras for electron microscopes, has enabled scientists to visualize the structure of proteins and determine the position of the atoms composing the proteins. This is a major breakthrough in biomedical sciences because it has enabled the discovery of the atomic structure of a whole new set of proteins. This information was recognized by the journal Nature Methods.
– Dr Fredda Branyon