Enteric and Diarrheal Disease

Ry Young III from Texas A&M AgriLife Research in the U.S. will engineer particles that resemble bacteria-infecting viruses (phage), but are functionally defective, for developing treatments that can more safely modify bacteria in the infant gut and thereby protect against disease and malnutrition. So-called lytic phage physically destroy the bacteria they infect and are considered to be potentially highly valuable for treating many childhood infectious diseases that are prevalent in developing countries and cause substantial morbidity and mortality.

Paul Bollyky from Stanford Medical School in the U.S. will study whether filamentous phage – viruses that infect bacteria – direct structural changes in the lining of the intestines and thereby promote the growth of healthy bacteria to protect against disease. Phage are considered to be a potentially rich therapeutic resource for infectious diarrhea and environmental enteropathy, which are prevalent in developing countries, but much remains to be learned about them.

Todd Parsley of SynPhaGen, LLC in the U.S. will engineer phage-like particles to transfer genes into specific bacteria in the infant gut that program them to produce therapeutic proteins that protect against environmental enteric dysfunction, which is a major cause of morbidity and mortality in developing countries. Rather than employing bacteria-infecting phage to destroy bacteria, they will engineer safer particles, which are unable to replicate and do not kill the bacterial host.

David Low from the University of California, Santa Barbara in the U.S. will engineer phage to selectively target and destroy several pathogenic bacteria to prevent enteric diseases in infants. Lytic phage infect bacteria and hold great promise as therapeutics for infectious diseases, but controlling their activity and preventing the development of bacterial resistance is challenging.

Martha Clokie from the University of Leicester in the United Kingdom will develop a bacteriophage to destroy the diarrhea-causing bacterium Shigella, and study its effect on microbial populations in the gut. Shigella is a leading cause of death in children under five years old in the developing world but there are no effective vaccines due in part to the many different forms of the bacterium. Phage are viruses that can destroy specific bacteria, and are an alternative approach to vaccines.

Srivatsan Raman of the University of Wisconsin-Madison in the U.S. will develop a platform for engineering synthetic phage - bacteria-infecting viruses - that can be easily reprogrammed to target specific bacterial species and that can be switched off to improve their safety for treating enteropathogenic diseases in newborns.