Clostridium difficile; Research and Development April 2014

Here’s the latest from the Clostridium difficile research community:
The importance of biofilm formation in chronic and recurrent infections across a cross-section of pathogens, including C. difficile has been studied in great detail. Whether biofilm formation in CDI is an important marker for recurrence is not clearly understood. Crowther et al compared germination, proliferation and toxin production between planktonic and sessile communities of C.difficile in a triple-stage chemostat gut model and here have reported that planktonic populations of C.difficile may be a reservoir for spore persistence and recurrence.
http://jac.oxfordjournals.org/content/early/2014/04/30/jac.dku116.long
Ransom et al have identified a gene cluster that is found exclusively in C.difficile and some closely-related species of bacteria that encode three cell division proteins: MldA, MldB and MldC. Mutant strains that lack the Mld proteins are severely attenuated for pathogenesis in a hamster model of CDI and thus are potential targets for therapeutics that can disrupt the spread of CDI.
http://jb.asm.org/content/early/2014/04/08/JB.00038-14.long
C.difficile are spores formers and the infectious unit for CDI is the spore. The proteins present on the outerlayer of the spores can be used as potential vaccine targets. Spore proteins present on the outer layer of spores, the exosporium, may be essential for the initiation and persistence of CDI. Three C.difficile collagen-like exosporium proteins (BclA) are expressed on the exosporium of the spore. Mutants of BclA proteins were reported to have aberrant structure and faster germination rates than wild type strains. Infection experiments done in mice suggest that BclA1 plays a role in the early stages of infection.
http://onlinelibrary.wiley.com/doi/10.1111/mmi.12611/abstract
C.difficile strains express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most strains and is a potential target for vaccine development. The efficacy of PSII glycoconjugate-based vaccine using recombinant fragments of toxin A and toxin B were studied in mice. This vaccine was immunogenic and able to illicit toxin neutralizing antibody, one of the correlates of protection against CDI.
http://www.mdpi.com/2072-6651/6/4/1385
The last decade has seen a rapid change in the epidemiology of CDI due to the emergence of so called ”hypervirulent”strains of C. difficile BI/NAP1/027 . Although it is still unclear what exactly contributes to this rapid spread of this strain, Robinson et al hypothesize that the rapid spread of these hypervirulent ribotype 027strains is due to increased fitness over the historic strains such as ribotypes (001, 002, 014, and 053). Looking at in vitro as well as an in vivo model of competition in mice, data suggests that these hypervirulent strains may be able to outcompete historic strains in a mixed infection/complex microbiota environment.
http://iai.asm.org/content/early/2014/04/08/IAI.01524-14.long

Chandrabali Ghose-Paul,MS,PhD, Chairperson of Research and Development