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Discovery boosts fight against infection

A breakthrough by an international research team led by scientists from the University of St Andrews could help fight deadly bacteria responsible for diseases like meningitis, blood disorders and hospital-acquired infections.

The scientists’ discovery of a novel bacterial protein complex may ultimately help in designing drugs to disable pathogens that cause a wide range of serious and common disorders, according to Professor James Naismith of the Centre for Biomolecular Sciences at St Andrews.

The research is published today in Nature. It is a joint effort involving St Andrews and the University of Guelph in Canada.

The research team described the first structure representing a previously unknown class of membrane proteins essential in allowing pathogens to elude host immune defences.

This protein – Wza – enables the bacteria to move large, complex sugar-containing molecules called polysaccharides through the cell membrane. Once on the cell surface, these long polymer chains make a protective “coat” against the immune system.

Prof Naismith said “This is the most strikingly beautiful structure I have seen in my career – the structure is dramatic and looks like a Greek amphora. It gives us a fascinating insight into this very important process.

“The structure manages a very difficult trick. Imagine two pieces of water separated by a layer of oil. Normally there is no way to move from one pool to the other, oil and water do not mix. “Wza takes the carbohydrate from inside the cell, keeps it very wet and allows it cross the oily outer layer of the bacteria. The key trick is Wza does this without creating a hole in the bacteria.”

Prof Chris Whitfield of the University of Guelph said “My lab has worked on the process of capsule formation for many years. This is a very exciting result which represents a massive step forward. It takes us from imagining how a complex process could possibly be achieved to a position where we can now develop specific questions about the process itself.

“The collaboration between Guelph and St. Andrews draws together two research teams with complementary skills and this has been critical for our success. The structure helps push forward a collaboration that has lasted over ten years.”

Professor Naismith added “The real credit goes to two of my colleagues, Changjiang Dong, (a post-doc researcher here) and Kostas Beis (a former PhD student, now an RCUK fellow at Imperial) who preserved with this difficult project. I also want to thank The Wellcome Trust, BBSRC and SFC who fund the lab.”

The discovery may give researchers a new target for antibiotics intended to prevent the polymers from passing through bacterial membranes. Alternatively, drug companies may devise new ways to keep large membrane channels fixed open – another strategy that may prove just as lethal to pathogens.

Note : A jpeg of the structure of Wza is available on request from Allison Irvine, University of St Andrews Press Office, tel 01334 462529, e-mail ai@st-andrews.ac.uk

Issued by the University of St Andrews. Contact : Niall Scott, tel 01334 462244, mobile 07711 223062

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