21 June 2012
Clostridium difficile [Credit: CDC/Dr. Gilda Jones]
Written by Laura Deakin
As a Ph.D student at the Wellcome Trust Sanger Institute, I have been investigating how Clostridium difficile bacteria are able to infect people for nearly four years. This bacterium, which is found in hospitals and is rife in the developing world, has been a hot topic of discussion in both the scientific literature and mainstream media in recent years.
C. difficile is the leading cause of antibiotic-associated diarrhoea in developed countries and has been responsible for a number of deaths in hospital patients. The bacterium releases spores that are highly infectious and cannot be killed by standard hospital cleaning routines. As a result C. difficile bacteria are now widespread in many hospitals and they are capable of causing major epidemics that are becoming increasingly frequent and severe.
To understand how the bacteria are able to infect people and transmit from one person to the next, I have been investigating the role of a gene called spo0A. Working with the C. difficile team at the Institute, I infected mice with C. difficile, to allow us to recreate and study many aspects of the disease; including its persistence and transmission in humans.
Using these mice as a model, we are able to mimic the transmission of C. difficile within hospitals and the effects of different techniques employed to minimise its spread. For example, we are able to explore the impact on transmission of patient-to-patient contact and shared rooms, and to study the effectiveness of patient isolation in lowering infection rates.
The study we published online in the journal Infection and Immunity looked at the role the spo0A gene plays in allowing C. difficile to transfer from person to person. We found that the bacterium had to have a normal version of the gene for it to be transmitted. The gene is essential for disease transmission.
Further study revealed that spo0A is also responsible for the persistent nature of C. difficile. This persistence is seen in patients who have been given vancomycin (a powerful antibiotic) to treat the disease. The treated patients recover and return home to an environment that contains C. difficile. The bacteria are then able to reinfect them, resulting in a second wave of disease. Some people can experience multiple episodes of infection over many years. Successful reduction of transmission would greatly reduce the threat of C. difficile as a cause of disease in hospitals.
Our findings suggest that the spo0A gene is a potential target for the development of therapies to disrupt or stop C. difficile transmission. The discovery of this genes role also has clinical implications relating to the management of patients in hospital to minimise transmission: for example by isolating infected patients and by using ‘barrier nursing’ (that is, the wearing gloves, gowns when treating the patients and employing heightened disinfection regimes).
This discovery is just the beginning: now that we’ve identified the importance of spo0A in transmission and persistence, we are now expanding our search to find other, related, genes that may also play a role. Finding these genes will allow us to identify points of intervention that might ultimately be used to contain the bacteria’s spore-mediated transmission and limit the spread of C. difficile.
Laura Deakin is a Ph.D student in the Microbial Pathogenesis team at the Wellcome Trust Sanger Institute... more
Paper: Deakin L et al. Clostridium difficile spo0A gene is a persistence and transmission factor. Infect Immun 2012. doi: 10.1128/IAI.00147-12