Disarming Type III Secretion System of Enteric Pathogens

Alessio Fasano of Massachusetts General Hospital in the U.S. will isolate bacteriophage (viruses that infect bacteria) that specifically kill pathogenic Escherichia coli and Shigella bacteria, which cause environmental enteropathy and other potentially deadly childhood diseases. They will perform a high-throughput screen using a diverse phage library to isolate phage that specifically target the type-III secretion system expressed by enteric pathogens like E. coli. They will also test an alternative approach by constructing phage to carry so-called CRISPR-Cas9 nucleases that they will engineer to target and cleave bacterial type-III secretion system genes. Results from both approaches will be tested for their capacity to selectively kill enteric pathogens and inhibit infection in a human organoid model, which consists of different cell layers to mimic the structure and function of the human gut.