A single sulfatase is required to access colonic mucin by a gut bacterium



Luis, Ana S, Jin, Chunsheng, Pereira, Gabriel Vasconcelos, Glowacki, Robert WP, Gugel, Sadie R, Singh, Shaleni, Byrne, Dominic P, Pudlo, Nicholas A, London, James A ORCID: 0000-0002-5823-7057, Basle, Arnaud
et al (show 11 more authors) (2021) A single sulfatase is required to access colonic mucin by a gut bacterium. NATURE, 598 (7880). 332-+.

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Abstract

Humans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a barrier that separates these microorganisms from the intestinal epithelium<sup>1</sup>. 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 degradation of the complex O-glycans found in mucins. In the distal colon, these glycans are heavily sulfated, but specific sulfatases that are active on colonic mucins have not been identified. Here we show that sulfatases are essential to the utilization of distal colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron. We characterized the activity of 12 different sulfatases produced by this species, showing that they are collectively active on all known sulfate linkages in O-glycans. Crystal structures of three 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 has a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by a prominent group of gut bacteria, an important process for both normal microbial gut colonization<sup>2</sup> and diseases such as inflammatory bowel disease<sup>3</sup>.

Item Type: Article
Uncontrolled Keywords: Colon, Animals, Humans, Mice, Bacteroides, Sulfatases, Acetylgalactosamine, Galactose, Mucins, Crystallography, X-Ray, Substrate Specificity, Models, Molecular, Female, Male, Gastrointestinal Microbiome
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 15 Nov 2021 08:22
Last Modified: 18 Jan 2023 21:24
DOI: 10.1038/s41586-021-03967-5
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3143083