Discovery and analysis of novel Francisella virulence factors

Francisella tularensis is a highly infectious bacterium with poorly defined mechanisms of pathogenesis. This thesis develops a transposon mutagenesis system for F. tularensis subsp. novicida, enabling identification of several novel virulence factors. Immunization with mutant derivatives of four factors protected mice from high‑dose wild‑type challenge, highlighting vaccine potential. One disrupted gene encodes tandem repeat motifs; a single repeat forms a stable, oligomeric domain that binds host E‑cadherin–associated factors and resembles adhesion domains in Staphylococcus aureus. These findings advance understanding of Francisella virulence, entry, and vaccine development.