Scientists close to cracking Clostridium difficile's shell
EU-funded scientists have produced the first-ever high resolution images of one of the proteins that forms a protective 'shell' around the notorious superbug, Clostridium difficile. The new knowledge of the shell's structure could lead to the development of new drugs and possibly even a vaccine against the bacteria. The study, published in the journal Molecular Microbiology, is partly funded through the NAS-SAP ('Nano arrayed systems based on self assembling proteins') project, which is financed through the 'Nanotechnologies and nano-sciences, knowledge-based multifunctional materials and new production processes and devices' Thematic area of the Sixth Framework Programme (FP6). Access to research infrastructures needed for the study was also supported through FP6. Clostridium difficile (C. difficile) cells are surrounded by a so-called surface layer (or 'S-layer') made up of two types of protein which link up to form a kind of jacket around the bacterium. The S-layer is thought to play an important role in enabling C. difficile to colonise the human gut, where it releases toxins. Crucially, the S-layer is vital to C. difficile's survival; without it, the cells soon die. The researchers hope that by shedding new light on the S-layer's make-up, they will identify structures that could be targeted by new drugs. The researchers, from Germany, the UK and Russia, used x-ray crystallography to create high resolution images of LMW SLP (low-molecular-weight S-layer protein), which, together with HMW SLP (high-molecular-weight S-layer protein), form's the bacterium's S-layer. In addition to this, the researchers produced lower resolution images which reveal how the two proteins link together to form a two-dimensional array. 'This is the first time anyone has gained detailed information about the molecular structure of C. difficile's protective 'jacket', because analysing the two protein components is painstakingly difficult work,' commented Professor Neil Fairweather of Imperial College London in the UK. 'We're confident that continuing this work to better understand the formation of this protective coat and its exact function will reveal new targets for effective drugs to beat this dangerous pathogen,' said Professor Fairweather, one of the authors of the study. The human immune system recognises the S-layer as a threat, and triggers an immune response when it encounters it. When the structure and function of the proteins that make up the S-layer are fully understood, the findings could lead to the development of a vaccine against C. difficile. The scientists now plan to produce high resolution images detailing the structure of the entire S-layer, and to further investigate the areas where the two proteins link together. C. difficile is naturally present in the gut of a small percentage of adults and about two-thirds of children. When people are healthy, it does not cause problems. However, when antibiotics are administered to treat other problems, the 'friendly' bacteria in the gut are often killed too, leaving the way open for C. difficile to multiply and cause disease. Because it is usually associated with antibiotic use, most cases occur in a clinical setting, and C. difficile is now the leading cause of hospital-acquired diarrhoea in Europe and North America. Worryingly, cases of disease associated with C. difficile are on the rise and the bug is already resistant to many antibiotics.
Countries
Germany, United Kingdom