Molecular analysis of Salmonella host specificity

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The aim of this research program focuses on defining the genetic basis of host-specificity in related bacteria with different host ranges. Our model bacterium is Salmonella enterica serovar Typhi (S. Typhi), which is host-resctricted (specific to only one host) in comparison to the well-studied S. enterica serovar Typhimurium that can infect many animal species. Bacterial cell envelope components are the first to interact with the surrounding environment. We are therefore investigating adhesion systems and iron-acquisition systems to understand fundamental aspects of bacterial adaptation and evolution. Our objectives will be to: 1) characterize S. Typhi adhesion systems; (2) identify and characterize the regulatory network of iron homeostasis and (3) to characterize and determine roles of iron-acquisition systems in host adaptation. These studies will employ newly developed molecular genetic tools for global gene expression, will involve the generation of mutant strains and the use of a broad range of methods including microbial genetics, molecular biology, biochemistry, immunology, cell biology, and microscopy. The multifaceted training environment will introduce trainees to a diversity of disciplines that will be an important asset for their development that should lead to successful careers in biological and natural sciences. It is anticipated that the research proposed in this application will contribute to our understanding of basic mechanisms of bacterial fitness, adaptation and evolution. This information should also provide important insights regarding the roles of bacterial adhesion and iron homeostasis. As some of the targeted systems are conserved among other bacteria, this may potentially lead to common strategies for prevention and treatment against many bacteria in different environments, both within the host and in environmental settings, such as in water and food sources.