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Stuck on you: Scientists lay bare secrets of bacterial attachment proteins

An unprecedented picture of how bacteria latch on to human cells has been published by UK, French and US scientists. They have produced a finely detailed model of one of the tools used by some of the nastiest varieties of the stomach bug, Escherichia coli, to stick to and gain entry to host cells.

Led by senior author Dr Stephen Matthews, Reader in Chemical and Structural Biology at Imperial College London, the research is published in the latest issue of the journal Molecular Cell (*See Notes to Eds).

Bacteria need to stick to a host cell, before colonising and attacking it, and causing infection. They do this with the help of proteins on their outer surface called adhesins and invasins. The former attaches itself to the host cell and the latter assists the invasion. Together they define how aggressive or virulent the bacteria are at attacking the host.

Most families of adhesins belong to bacteria that cause a single disease, but the 'Dr' family of Adhesins makes far more trouble: it is responsible for chronic diarrhoeal, intestinal and urinary tract infections, and is similar to some present in strains of Salmonella.

The researchers characterised the way in which the Dr Adhesins help bugs to cause multiple diseases because they use a very common receptor on the host cell membrane as an anchor point to attack. They target a receptor responsible for regulating one of the important human immune responses, known as Decay Acceleration Factor, or DAF.

"Cell adhesion is one of the first contacts between bacteria and host," said Dr Matthews. "Knowing the architecture of the bacteria target allows us to conceive ways to disrupt this adhesion, which may lead to potential therapeutic intervention."

Dr Matthews' team at Imperial used nuclear magnetic resonance (NMR) spectroscopy to yield detailed insights into the structure of the two nanometre-wide Dr Adhesins.

Their work helps to resolve a long-standing debate amo
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1-Sep-2004


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