Grant: Project Grant

Mucus is a sticky substance that coats the inner lining of the gut. Made of proteins covered in sugars, mucus forms a kind of slippery wall that prevents the bacteria, viruses and food antigens found inside the gut, from escaping and causing damage throughout the body. Also, good bacteria found in the gut can graze on the sugars within the mucus, releasing them so that they, and other nearby good bacteria can feed. Keeping these good bacteria well fed is known to help promote gut health. My lab recently discovered that certain dangerous gut bacteria have developed sneaky ways to take advantage of the mucus grazing bacteria. The dangerous bacteria steal their mucus sugars, using them as fuel to grow to large numbers in the gut. They also use these sugars as signals to attack the mucus layer, burrowing across the mucus until the escape and cause disease. Developing a better understanding of how this occurs could help us prevent the damage caused by dangerous gut bacteria. In this study, we will use a special type of bacteria called Citrobacter that can only infect the intestines of mice. We will test which sugars are the most important to Citrobacter, and also test different types of Citrobacter that are unable to use these sugars, to see how this impairs their ability to cause disease. We will also use germfree mice that have no bacteria in their intestines, testing how this affects Citrobacter's ability to access mucus sugars. Specific types of mucus grazing bacteria will be given to these mice, to test how this affects mucus sugar levels, Citrobacter's ability to cause disease, and where Citrobacter is found in the gut. Lastly, we think the best way to prevent Citrobacter and other dangerous bacteria from causing disease is by limiting their access to mucus sugars. We will test how giving mucus grazing bacteria another food source (ie. fiber) affects mucus sugar levels and if this alters the ability of Citrobacter to cause intestinal disease.