Molecular characterization of Salmonella host specificity

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The aim of this research program is to define the molecular and genetic basis of host tropism in related bacteria. Our bacterial model is Salmonella enterica, one of the leading foodborne bacterial pathogens in Canada. Salmonella strains are classified into serovars, some are specific to only one host, whereas others can colonize multiple host species. There are 2600 serovars and there is no way yet to predict their host range or virulence. We propose to compare and study a serovar that is specific only to humans, the host-specific S. Typhi and a broad-host range serovar, the generalist S. Typhimurium. We have already observed many phenotypic differences between these serovars and we will pursue by identifying genes involved in host adaptation. Biofilm is an adaptation mechanism in which the bacterium is embedded in an extracellular matrix to protect itself and persist. In Salmonella, the generalist produces biofilm in the environment while the host-specific serovar produces biofilm within the host. The major components of the biofilm matrix, cellulose and the curli adhesin, are not expressed by the host-specific serovar. We have demonstrated that the generalist produces less biofilm in the presence of bile, a substance found in the gut, whereas the host-specific serovar produce more biofilm in the presence of bile. Thus, we hypothesize that biofilm formation is critically linked to host specificity. We will investigate and compare biofilm produced by either the generalist or the host-specific serovar. First, we will characterize Salmonella biofilms in the presence of bile by determining the biomass, the matrix composition, organization and viability. Innovative, qualitative and quantitative approaches will be used to observed biofilm formation in real-time. We will then identify key factors involved in biofilm formation using a high-throughput robotic platform. We will also investigate the influence of microbiota on biofilm formation. Finally, we will investigate the influence of host cell type and origin on Salmonella biofilm formation. Comparison between these two distinctly adapted serovars will lead to the identification of key components that should shed light on specific mechanisms of host adaptation. It is anticipated that the research proposed in this application will contribute to our understanding of basic mechanisms of bacterial biofilm formation and species evolution. As some of the targeted systems are conserved among other bacteria, this may potentially lead to common strategies to potentially reduce the presence of such bacteria in different environments, both within the host and in environmental settings, such as in water and food sources.