Elucidating Molecular Interactions of Shigella Type Three Secretion System Components Critical for Pathogenesis

Shigella are pathogenic bacteria which commonly infect human hosts through the fecal-oral route. As the causative agent of shigellosis, a disease characterized by severe diarrhea, nausea, and vomiting, Shigella are responsible for an estimated 90 million infections and 100,000 deaths each year. With the emergence of antibiotic resistant strains of Shigella, the need for alternative treatments methods has become critical to fighting outbreaks of shigellosis and drug resistant strains. One such method is to target the infection system of the bacteria, called the type three secretion system (T3SS). The T3SS includes a complex needle and syringe-like apparatus that is used to interact and infect host cells, which if better understood, could aid in treating and preventing infection. The Dickenson lab at Utah State University has identified and characterized the powerhouse of the T3SS, the ATPase Spa47, and has found it to be critically necessary for needle formation, secretion, and ultimately Shigella virulence. Additionally, studies into the interaction between the apparatus tip proteins IpaB and IpaC and host membranes have revealed a localization dependence on host membrane structure and composition. Studies into both the apparatus ATPase and tip proteins help to further our current understanding of the Shigella infection system and provide a foundation for future drug and vaccine trials as Spa47, IpaB, and IpaC are shown here to be promising therapeutic targets