Spore draw: Fighting C.diff infections
Clostridium difficile has become one of the most worrisome public health threats of the 21st century. Commonly seen in healthcare settings, cases have leapt tenfold in the last decade. C. difficile is both highly infectious and difficult to eradicate - traits that, research at the Wellcome Trust Sanger Institute has revealed, are linked to the durability of its spores.
To get a better picture of C. difficile transmission, Trevor Lawley, Gordon Dougan and colleagues have established a model hospital environment with mice as 'patients'. When C. difficile was introduced, it colonised the intestines of mice without causing any symptoms.
The mice shed spores, but did not infect others living with them. However, when treated with antibiotics, the mice become highly infectious 'supershedders', releasing vast numbers of spores that rapidly spread disease through the mouse community (ref. 1).
The sudden change occurs because antibiotic treatment kills most of the naturally occurring bacteria in the gut, opening up an environment that C. difficile can rapidly colonise. When antibiotic treatment is halted, the gut bacteria recover and displace C. difficile (although some animals remain supershedders for several months).
The work highlights the importance of non-pathogenic gut bacteria in keeping C. difficile under control. In theory, manipulating the gut's microbial ecosystem - promoting the growth of harmless bacteria - could provide a way to manage C. difficile. Indeed, the gut bacteria present in mouse faecal material can be used to inoculate animals and suppress C. difficile. Although this is not a practical option for people, it may be possible to identify which bacterial species are most effective at suppressing C. difficile and use them in a form of 'bacterial therapy'.
The Sanger Institute team has also been able to purify spores, enabling a proteomic analysis to be carried out (in conjunction with Jyoti Choudhary and the Sanger mass spectrometry team).
This has revealed hundreds of spore-associated polypeptides, many seen across the Clostridium family but some specific to C. difficile (ref. 2). Ultimately, a greater understanding of the make-up of the spore will provide leads towards better diagnostics and vaccines.
The team is also looking at how spores are affected by widely used disinfectant techniques. While spores are eradicated by highly oxidising approaches such as vapourised hydrogen peroxide ('deep clean'), many cleansing products have worryingly little effect. Collaborations are now being established with hospitals to identify ways to use the new findings to track and, it is hoped, to block the spread of C. difficile.
Image: Clostridium difficile
References
1 Lawley TD et al. Infect Immun 2009;77(9):3661-9.
2 Lawley TD et al. J Bacteriol 2009;191(17):5377-86.