Grant: Project Grant

Intestinal mucus is a mix of proteins and sugars. It coats the inner surface of mammalian intestines, lubricating the passage of food and stool along the length of the gut. In addition, mucus acts as a barrier, keeping the vast community of resident, and largely peaceful bacteria from escaping the intestine and causing damage. My group has been exploring if mucus has other functions, by infecting mice with disease causing bacteria called Citrobacter, relatives of the bacteria that cause "hamburger disease". We have been comparing how well Citrobacter infects mice that produce mucus, with mice that are lacking mucus, or mice that lack key mucus sugars. We know that when Citrobacter enters the gut, it has to compete with resident bacteria for space and food. Normally it can take up to 1 week for Citrobacter to outcompete the resident bacteria, expand in number and cause disease. Interestingly, when Citrobacter infects mice lacking mucus, or key mucus sugars, it bypasses the resident bacteria, spreading through the gut and causing disease almost immediately. We found that the resident bacteria in these susceptible mice are very poor at producing a fatty acid called butyrate, but when we add butyrate back, the mice showed improved protection against Citrobacter. We will explore how resident bacteria use mucus sugars to produce butyrate, and define how loss of mucus impacts Citrobacter-host interactions. In addition, we know that as Citrobacter infection progresses in normal mice, some of the cells that line the gut produce significantly more mucus, presumably to thicken the protective mucus barrier and further protect the gut, as well as flush away some of the Citrobacter. It is unclear however, to what degree this mucus response actually protects the host, which cells participate in the response, and finally, whether this release of mucus reflects the direct actions of the cells that make mucus, or if they need to be activated by cells of the immune system.