Heterologous Reconsitutition of the Quorum Sensing System of Clostridium Difficile in Non-Pathogenic Hosts

It has recently been discovered that toxin secretion in hypervirulent strains of Clostridium difficile, a highly antibiotic-resistant opportunistic pathogen, is upregulated by a 2-component quorum sensing apparatus, leading to increased mortality in patients infected with these strains. In this work we reconstitute the quorum sensing system of C. difficile in non-pathogenic hosts. We discuss synthetic strategies to systematically isolate responsive regulators and development of high-throughput screens for detection of quorum sensing signaling molecules. Finally, we reconstitute a homologous system from the food-borne pathogen Listeria monocytogenes and examine implications of orthogonality and cross-talk between gram-positive QS in pathogens.