Genetic requirements for Listeria monocytogenes survival and persistence
We also investigate the genetic requirements for Listeria monocytogenes survival and persistence during systemic infection, using a novel approach “induction transposon insertion sequencing” (InducTn-seq). InducTn-seq bypasses highly restrictive host infection bottleneck by generating mutants within the animals, enabling genome scale forward genetic screen in vivo. We will leverage InducTn-seq to investigate the pathogen genetic requirements in the infection sites with stringent host-imposed bottleneck, including the gallbladder, a pathogen reservoir initiated by a single L. monocytogenes cell.
Function of infection-stimulated bile metabolites
The liver receives the majority of its blood supply from the portal venous system, which drains the gastrointestinal tract. In return, the liver communicates with the intestine by forming and secreting bile into the intestine. We recently discovered that enteric pathogens stimulate hepatic synthesis of a shared set of proteins and metabolites that are secreted in bile and mediate host defense in the intestine. We will utilize a multidisciplinary discovery pipeline that consists of next-generation sequencing based receptor screen, bacterial genetics, host genetics and metabolomics to characterize the molecular mechanisms that underpinning the defense and immunoregulatory function of bile components.
