Completed Infection & Immunity Genetics & Molecular Biology

Understanding the Molecular Basis of Virulence in Clostridium difficile.

Funder MRC (part of UKRI)
Recipient organisation University of Nottingham
Funding £1.6M
Period Sept 2007 — Mar 2013

In plain English

AI plain-English summary

C. difficile bacteria produce toxins that punch holes in the lining of the human gut, causing severe diarrhoea that can kill elderly patients in hospital. The problem is that while scientists have the complete genetic blueprint of C. difficile, they do not know which genes actually drive its ability to cause disease. Without that knowledge, developing new treatments or infection-control measures is guesswork. The researchers have now built the tools to systematically switch off individual genes and watch what happens—something that was previously impossible for this bacterium. If this work succeeds, it will reveal the specific molecular machinery C. difficile uses to infect, multiply, and damage human tissue. That knowledge could eventually lead to targeted drugs that disable the bacterium without wiping out the rest of the gut microbiome, or to better diagnostic tests that identify dangerous strains early. For now, the research is fundamental science: it is asking how a pathogen works at the molecular level. Past discoveries of bacterial virulence mechanisms have led to vaccines, antibiotics, and infection-control protocols that now save thousands of lives.

View original technical description
There are currently heightened public concerns over infection rates in UK hospitals, and in particular those caused by so called ?superbugs? that have become resistant to available antibiotics. One such bug is Clostridium difficile. It causes debilitating diarrhoea, which in extreme cases can kill. It mainly affects the elderly. As this proportion of the population is increasing, the disease is becoming more common. Worryingly, a new, even more deadly variant has now arrived in Europe from North America. Aside from the human suffering, it costs the NHS over #402 million per year, and now is responsible for more deaths per year than MRSA. To control infections, we need to understand how an organism causes disease. Under Wellcome Trust sponsorship, the complete genome sequence of the organism (ie., its genetic blueprint) has been determined. However, whilst we now know the sequences of every gene in the C. difficile chromosome, we do not understand what they are doing. The best way of working out what genes do, is to mutate them (make them non-functional) and assess the consequences. Until now this has not been possible. We have now developed the tools needed, and wish to use them to better understand how this bug causes disease. This should eventually lead to better ways of controlling the disease.

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Researchers

Adam Roberts (Co-Investigator)Alan Cockayne (Co-Investigator)Nigel Minton (Principal Investigator)Peter Mullany (Co-Investigator)

Related Research

Grants with similar aims, by meaning.

Development of intergrative technology for gene inactivation in Clostridium difficile
Investigating molecular mechanisms of Clostridium difficile colonisation
Molecular and genetic dissection of Clostridium difficile spore-mediated transmission to identify points of intervention
Structure-function studies on Clostridium difficile large toxins
Understanding the relationship between bacteriophages and pathogenicity in the gut pathogen Clostridium difficile

Original classification

Research Grant

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