A key mechanism by which a bacterial pathogen causes the deadly tropical disease melioidosis has been discovered by an international team of scientists.
The findings are published today in the journal Science and show how a toxin produced by the bacterium Burkholderia pseudomallei kills cells by preventing protein synthesis. The study, led by the University of Sheffield, paves the way for the development of novel therapies to combat the bacterium which infects millions of people across South East Asia and Northern Australia.
Using intense X-rays at Diamond Light Source, the UK's national synchrotron facility, and at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France, the research team solved the structure of a protein from Burkholderia, the function of which was initially unknown.
"The information gathered from the structure suggested that the protein was a previously unsuspected toxin and sparked a search for its mode of action. This eventually led to the discovery of how it prevents human cells from making proteins and helped us to understand how it causes cell death," says research lead Professor David Rice from the Department of Molecular Biology and Biotechnology at the University of Sheffield.
Melioidosis, along with HIV and tuberculosis, is one of the top three causes of death by infectious disease in parts of South East Asia and arises from infection by the bacterium which thrives in water and warm, moist soils and can enter the body through the lungs or through open wounds.
It causes either an acute form of the disease which presents immediately upon infection, or it can lay dormant in the body emerging many years, and often decades, later. In the acute form of the disease, even with a long course of treatment, mortality rates in endemic areas can be as high as 40 per cent. With a wide range of symptoms, melioidosis can be difficult to diagnose, hampering medical intervention
|Contact: Clare Elsley|
University of Sheffield