Grant: Project Grant

The cells that line our intestines have many functions, including making and releasing mucus. Mucus is made up of proteins that are covered with sugars, and it creates a thick and slimy layer that coats the whole inner surface of our intestines. The mucus layer is our "first line of defense" against food and water-borne disease causing bacteria - such as the dangerous "Hamburger disease" causing E. coli bacteria that cause bloody diarrhea and kidney failure. To inflict disease, these bacteria have to move across the mucus layer and enter the body. We propose that intestinal mucus plays an active role in determining whether dangerous bacteria can infect their hosts. We have found that during infection, intestinal cells make more mucus and they also increase the content of certain sugars found on the mucus. This led us to predict that these mucus changes may (a) protect the host by pushing the bacteria away from the intestinal lining, and/or (b) the mucus may provide additional nutrients (the sugars) for the dangerous bacteria, reducing their need to invade and damage the intestine to obtain food. In this project, we will investigate the role of mucus, by studying how the immune system causes these changes in the mucus. We will also study what parts of the mucus layer are most important in providing protection, and what happens to dangerous bacteria when the mucus layer is missing. We will also test whether changing the ability of the E. coli bacteria to use sugars as food, or changing the availability of these sugars affects how much damage the bacteria cause to the intestine. This project addresses an understudied, yet critical aspect of intestinal defense and will test if modifying the levels of sugars in mucus offers a new way to fight dangerous gut infections by targeting bacterial pathogen nutrition.