Back to Search
Start Over
A single bacterial sulfatase is required for metabolism of colonic mucin O -glycans and intestinal colonization by a symbiotic human gut bacterium
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- SummaryHumans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a physical barrier that separates these microbes from the intestinal epithelium. Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate the degradation of the highly complex O-glycans found in mucins. In the colon, these glycans are heavily sulfated, but the specific sulfatases that are active on colonic mucins have not been identified. Here, we show that sulfatases are essential to the utilization of colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron. We have characterized the activity of 12 different sulfatases encoded by this species, showing that these enzymes collectively are active on all of the known sulfate linkages in colonic O-glycans. Crystal structures of 3 enzymes provide mechanistic insight into the molecular basis of substrate-specificity. Unexpectedly, we found that a single sulfatase is essential for utilization of sulfated O-glycans in vitro and also plays a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by gut bacteria, an important process for both normal microbial gut colonization and diseases such as inflammatory bowel disease (IBD). Sulfatase activity is likely to be a keystone step in bacterial mucin degradation and inhibition of these enzymes may therefore represent a viable therapeutic path for treatment of IBD and other diseases.
- Subjects :
- chemistry.chemical_classification
0303 health sciences
Glycan
biology
Chemistry
Sulfatase
030302 biochemistry & molecular biology
Mucin
biology.organism_classification
Mucus
Intestinal epithelium
03 medical and health sciences
Biochemistry
biology.protein
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Glycoprotein
Bacteroides thetaiotaomicron
Bacteria
030304 developmental biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....210f8866e144aeddd9dc8be386b7e571