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Scientists unlock the secrets of C. difficile's protective shell

The detailed structure of a protective 'jacket' that surrounds cells of the Clostridium difficile superbug, and which helps the dangerous pathogen stick to human host cells and tissues, is revealed in part in the 1 March issue of Molecular Microbiology.

Scientists hope that unravelling the secrets of this protective layer's molecular structure might reveal possible targets for new drugs to treat C. difficile infections.

The 'jacket' is a surface layer, or 'S-layer', made of two different proteins, with half a million of each covering every C. difficile cell. The S-layer is believed to help C. difficile cells colonise the human gut, where they release sickness-causing toxins.

The new research was led by scientists from Imperial College London, funded by the European Union Seventh Framework Programme and the Medical Research Council. They used X-ray crystallography techniques to produce the first ever high-resolution images of the structure of LMW-SLP, one of the two proteins that make up C. difficile's S-layer. The team also produced lower resolution images of the two S-layer proteins linked together into the 'building block' which makes up the layer over all.

Understanding exactly how the S-layer is formed, and how it works, could reveal new ways of fighting C. difficile infections, because without the S-layer, the pathogen cells cannot function, and die. The team behind the new study say that the long term aim is to use this structural knowledge to design a drug that will target the S-layer, leading to cell death, and the defeat of infection.

In addition, the research team behind today's study say that understanding the S-layer could be the key to developing a preventative vaccine for C. difficile. This is because the protein outer-shell of the pathogen is 'seen' and recognised as dangerous by the human immune system, triggering an immune response. This m

Contact: Danielle Reeves
Imperial College London

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