University of Virginia Health System

The genomes of ~120 human and animal microbial pathogens have been or are in the process of being completely sequenced. With this wealth of genetic information, there is a growing need for simple and innovative systems to explore bacterial and fungal virulence strategies and assay the contribution of individual genes to pathogenesis. Recent efforts have demonstrated that many mammalian pathogenic microbes can infect and cause disease in a number simple invertebrate hosts, including the model genetic organisms Caenorhabditis elegans. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. Similarly, features of the C. elegans germ-line encoded host defense system known as innate immunity have also been evolutionarily conserved across phylogeny. Our research program is focused on using C.elegans -based pathosystems to study the genetic and molecular mechanisms of microbial virulence and host defense response in several of today’s most important opportunistic human pathogens.

Project One –Staphylococcus aureus and other Gram positive pathogens
We have found that a number of clinically important Gram positive human pathogens infect and kill C. elegans. Remarkably, many of the virulence mechanisms employed by these microbes to cause disease in mammalian hosts have also been shown to be required for full pathogenicity in nematodes. Focusing on Staphylococcus aureus, we have found that C. elegans roundworms die over the course of several days while feeding on bacterial lawns and this killing is the result of an active infectious process. Staphylococcal virulence factors important for disease in both nematodes on vertebrates include proteases, hemolysins and N-acetylglucosamine (biofilm) as well as the gene regulators and metabolic systems that influence their expression. We are using the C. elegans host in mutation-based screening systems to identify and study novel virulence-related bacterial determinants.