Friday, 12 September 2014

First crystal structure of the C. difficile surface protein

Clostridium difficile is a major problem as an aetiological agent for antibiotic-associated diarrhea. The mechanism by which the bacterium colonizes the gut during infection is poorly understood, but undoubtedly involves a myriad of components present on the bacterial surface. This study provides some insights that may help in developing a new type of drug to treat the infection.

Researchers reported the first crystal structure of the C. difficile surface protein Cwp84. This cysteine protease enzyme is found on the surface of the bacterium and assists with production of the microbe's surface-layer, which is likely to play an essential step in the colonisation of the gut. The enzyme cleaves a single polypeptide (surface-layer protein A; SlpA) into low- and high-molecular-weight subunits.

Scientists have identified three critical regions in a mutant of the enzyme that could represent novel targets for drugs to attack C. difficile by blocking maturation of its surface layer during colonisation.

For further details, see:

William J. Bradshaw, Jonathan M. Kirby, Nethaji Thiyagarajan, Christopher J. Chambers, Abigail H. Davies, April K. Roberts, Clifford C. Shone, K. Ravi Acharya. The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein fromClostridium difficile. Acta Crystallographica Section D Biological Crystallography, 2014; 70 (7): 1983 DOI: 10.1107/S1399004714009997

Posted by Tim Sandle