C. diff. Research and Development – August 2015

Microbiota and Subsequent Effects on Colonization Resistance against Clostridium difficile

Alyxandria M. Schubert, Hamide Sinani, Patrick D. Schloss

To read this paper in its entirety :

http://mbio.asm.org/content/6/4/e00974-15.short?rss=1&ssource=mfr

The gastrointestinal tract harbors a complex community of bacteria, known as the microbiota, which plays an integral role preventing its colonization by gut pathogens. This resistance has been shown to be crucial for protection against Clostridium difficile infections (CDI), which are the leading source of hospital-acquired infections in the United States. Antibiotics are a major risk factor for acquiring CDI due to their effect on the normal structure of the indigenous gut microbiota. We found that diverse antibiotic perturbations gave rise to altered communities that varied in their susceptibility to C. difficile colonization. We found that multiple coexisting populations, not one specific population of bacteria, conferred resistance. By understanding the relationships between C. difficile and members of the microbiota, it will be possible to better manage this important infection.

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The spore-associated protein BclA1 affects the susceptibility of animals to colonization and infection by Clostridium difficile

To read this paper in its entirety :

http://onlinelibrary.wiley.com/doi/10.1111/mmi.12611/abstract

The paper shows that so-called “hypervirulent” strains of C. difficile, such as the 027 ribotype strains, are actually less infectious than the existing strains of C. difficile carried in humans and animals. We were able to show this by characterizing one gene of C. difficile that encodes the BclA1 protein. BclA1 is involved in the early stages of colonization and its presence enables spores of C. difficile to colonise the host. When this protein is removed or truncated the ability of spores to colonise is much reduced. This then raises the question of how hypervirulent strains are more efficient at infecting a host, in other words, how they can be more virulent. The answer is probably the hypervirulent strains are able to produce more toxins. This work raised the concept that C. difficile is similar to influenza. For example, with influenza the most infectious influenza strains  do not normally cause fatality (ie, the seasonal flu strains). On the other hand, the pandemic strains (avian influenza) are not very infectious (that is, they spread poorly) yet when they do infect they cause a dangerous infection more likely to lead to fatality. C. difficile we reason behaves in a similar way, the hypervirulent strains are poorly infectious yet cause a more potent infection while highly infectious strains cause a less potent infection. We plan to use this knowledge to type new isolates of C. difficile and assess their risk to humans.

Professor Simon M. Cutting
School of Biological Sciences,
Bourne Laboratories, 4-26,
Royal Holloway, University of London
Egham,
Surrey TW20 OEX
UK