Compositions and methods for treating clostridium difficile infection

Abstract

infection is the leading cause of hospital acquired antibiotic-associated diarrhea in the US (Bartlett, in 2006). The increased prevalence of circulatingstrains poses a significant health threat to US health care facilities. Strains expressing the toxinTransferase (CDT), in addition to Toxins A and B (TcdA and TcdB), are more virulent and are associated with higher mortality rates (Bacci et al., 2011). We recently identified a protective role for eosinophils againstpathogenesis (Buonomo et al., 2016). We have also defined CDT's ability to increase host inflammation and suppress protective eosinophils through a TLR2 dependent mechanism (Cowardin et al., 2016). How CDT promotes virulence and eosinophil suppression via TLR2 is still under investigation. We employed a genome-wide microarray approach to reveal divergent transcriptional profiles between protected (TLR2−/−) and unprotected (WT) mice infected with either CDT expressing or CDT mutant strains of. This work revealed novel host mediated TLR2-dependent inflammatory pathways to CDT. We provide an unbiased framework for understanding the host immune response to the binary toxin CDT produced byand how TLR2 signaling enhances virulence.