Carbohydrate sulfatases: a role in chronic bowel disease?

The mucus lining of the large colon forms a protective barrier between the bacterial community that inhabits the colon and the epithelial layer. Both experimental elimination, or excessive degradation of this mucus layer by colonic bacteria, leads to inflammation and thus chronic disease of the colon. Inflammation of the colon also increases the risk of colon cancer as well as being a precursor to it.

Colonic mucin is a glycoprotein which is ~80% carbohydrate by mass with these carbohydrates being heavily sulfated. The bacterial community in the distal colon are essential to human health, and metabolism of mucin, acts as a key nutrient and colonisation factor but excessive degradation leads to disease. Carbohydrate sulfatases have been identified as key enzymes for bacteria to utilise colonic mucin. Furthermore, key sulfatases have been identified as exo acting and both cell surface exposed and periplasmic making them excellent drug targets to inhibit and thus, control mucin metabolism in individuals with inflammatory bowel disease.

Here we propose an integrated molecule-to-function approach to:
1) Define structural features of bacterial carbohydrate sulfatases that determine substrate specificity
2) Identify which carbohydrate sulfatases elicit digestive tract disease
3) Identify small molecules that modulate sulfatase function.