CRISPR-Cas-Directed Bacteriophage Treatment of Enteropathogenic Escherichia coli (EPEC) Diarrhea

Haiqing Sheng and collaborators Carolyn Bohach and Scott Minnich from the University of Idaho in the U.S. will exploit the CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) system in a dual approach to combat enteropathogenic Escherichia coli (EPEC) infections. EPEC cause diarrhea and result in several hundred thousand infant deaths annually. They will engineer a CRISPR-Cas9 cassette to recognize and cleave a DNA sequence found specifically in EPEC, which will lead to selective EPEC cell death in the intestinal tract without affecting other beneficial bacteria. The engineered CRISPR-Cas9 will be administered using both safe EPEC-targeting viruses (bacteriophage) to treat primary infections as well as probiotic E.coli to stably establish the EPEC-targeting plasmid in the gut and block re-infection. They will test it using an established rabbit model of EPEC infection, which will pave the way for future clinical testing.