Principal Investigator (PI)
University of Washington
The Foundation is providing £166,037 in support.
Mayumi Holly
Technical assistance with the inhibitor screen including help with instruments and software. Access to GSK’s small molecule libraries. Extensive communication and advice regarding screen design, execution, troubleshooting, and compound identification.
The primary goal of this proposed project is to test the hypothesis that small molecule inhibitors of Shigella transcription factors can promote the rapid resolution of infection. Previously, data collected from an in vivo transposon library screen (TN-Seq) using a guinea pig model of shigellosis was performed to provide a global view of genes and pathways that are critical for Shigella to survive and compete within the host. Disrupting the expression of these crucial genes and pathways with small molecule inhibitors is expected to result in severe defects in Shigella’s ability to colonize the host and cause disease. The proposed project will use high throughput assays to screen compound libraries for inhibition of pathways deemed to be essential for Shigella to survive in the host. Identified hits will be validated and tested for their capacity to functionally alter the course of Shigella infection using established in vivo models. If successful, this strategy could act as a blueprint for developing new drugs that target essential survival pathways in microorganisms, leading to an entire new class of treatments against infectious diseases.