Shigella is a significant global pathogen that causes devastating infection rates every year. Shigella infects the gastrointestinal tract to cause diarrhea or dysentery. Our research aims to improve our understanding of infection to help develop more effective therapeutics like vaccines and other antimicrobial products.
First, animal models and emerging tissue culture techniques allow us to better understand the physiology of Shigella infection and faithfully reproduce the complexity of the human GI tract. Second, characterization of clinical Shigella isolates has helped to capture the diversity of this genus, identify important virulence genes, and improve our understanding of infection. We have used gastrointestinal signals like bile salts and glucose to understand how Shigella survives transit in the small intestine and regulates virulence gene expression for infection in the large intestine.
We have demonstrated how Shigella resists bile salts and have shown that Shigella produces adherence proteins to help initiate contact with epithelial cells to start infection. These protocols are designed to look at key aspects of epithelial infection like adherence, invasion, and intracellular survival of Shigella. We are performing these protocols using a standard epithelial cell line, but have also adapted the methods for sophisticated human GI models that are now available.
These protocols consider each phase of infection independently, which is critical to understand the key steps in Shigella infection. They also highlight that combined analyses can facilitate a greater understanding of Shigella infection at a holistic level.