Clostridium difficile Research and Development; April/May 2014

Here’s the latest from the Clostridium difficile research community:

April/May 2014
The role of probiotics in the treatment or the prevention of C. difficile infection (CDI) has not been clearly defined as yet. To study the role of Lactobacillus strains on the quorum-sensing signals and toxin production of C. difficile, Yun et al. looked at in vitro and in vivo effects of L. acidophilus strain or cell extracts. The results show that L. acidophilus GP1B can inhibit the growth of C. difficile and contribute to the survival of mice given C.difficile.

http://www.ncbi.nlm.nih.gov/pubmed/24856984
The endospores of Bacillus subtilis (B. subtilis) can serve as a tool for surface presentation of heterologous proteins in addition to acting in the role of a probiotic. The utility of B .subtilis as a probiotic was studied in a mouse model of CDI to show that oral administration of B. subtilis spores, especially when administered post infection, was able to attenuate symptomatic disease.
http://onlinelibrary.wiley.com/doi/10.1111/1574-6968.12468/abstract;jsessionid=9FC710353826E4D1D9F189D956C28DA7.f03t03
C. difficile flagellar proteins play a myriad role in pathogenesis from adherence, toxin production, and biofilm formation. Barketi-Klai et al looked at the global gene expression profiles of C.difficile fliC mutants and compared gene expression levels to those of the parent wild-type strain. fliC mutants strains led to the up-regulation of genes involved in mobility, expression of virulence factors and sporulation which was not seen with the wild-type mutant strain. The authors conclude that deregulation of fliC expression could lead to the upregulation or deregulation of other genes that enhance the pathogenecity of such strains.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0096876
In addition to a patient’s health, CDI is also a huge financial burden to patients, hospital and society. A recent study looked at the added costs of CDI on cardiac surgical patients using the Nationwide Inpatient Sample (NIS) database, and reported that in cardiac surgery alone, CDI adds an incremental cost of $212 million/year.
http://www.sciencedirect.com/science/article/pii/S0022522314004413
The spores of C.difficile are important in the pathogenesis of CDI. Spore proteins present on the outer layer of spore may be essential for CDI. The BclA proteins are glycolipids present on the spore surface and may be glycosylated by sgtA, which is cotranscribed with BclA3. Mutant strains of sgtA were not different from wild-type strains in terms of sensitivity to ethanol or lysozyme, but showed a change in heat-resistance and the ability to be internalized by macrophages.
http://jb.asm.org/content/early/2014/05/05/JB.01469-14.long

 

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