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A single sulfatase is required to access colonic mucin by a gut bacterium
- Source :
- Nature, Nature, Nature Publishing Group, 2021, 598 (7880), pp.332-337. ⟨10.1038/s41586-021-03967-5⟩, NATURE
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- International audience; Humans have co-evolved with a dense community of microbial symbionts that 34 inhabit the lower intestine. In the colon, secreted mucus creates a physical barrier that 35 separates these microbes from the intestinal epithelium. Some gut bacteria are able to 36 utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, 37 it remains unclear which enzymes initiate the degradation of the highly complex O-38 glycans found in mucins. In the colon, these glycans are heavily sulfated, but sulfatases active on colonic mucins have not been identified. Here, we show that sulfatases are essential to the utilization of colonic mucin O-linked glycans by the human gut symbiont Bacteroides thetaiotaomicron. We 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 and even possess the ability to cleave additional linkages not yet known to occur in host 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 Oglycans 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 like 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 :
- Male
Models, Molecular
Glycan
Acetylgalactosamine
Colon
[SDV]Life Sciences [q-bio]
Crystallography, X-Ray
Article
Substrate Specificity
Mice
03 medical and health sciences
Animals
Bacteroides
Humans
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Multidisciplinary
biology
Glycobiology
Sulfatase
030302 biochemistry & molecular biology
Mucin
Mucins
Galactose
biology.organism_classification
Mucus
Gastrointestinal Microbiome
Biochemistry
chemistry
biology.protein
Female
Sulfatases
Glycoprotein
Bacteroides thetaiotaomicron
Bacteria
Subjects
Details
- Language :
- English
- ISSN :
- 00280836 and 14764679
- Database :
- OpenAIRE
- Journal :
- Nature, Nature, Nature Publishing Group, 2021, 598 (7880), pp.332-337. ⟨10.1038/s41586-021-03967-5⟩, NATURE
- Accession number :
- edsair.doi.dedup.....be5d1ca9f1f704e9993e1ee810739da5