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

DOI: 10.1038/s41586-021-03967-5

Authors: Ana S. Luis (University of Michigan; University of Gothenburg) , Chunsheng Jin (University of Gothenburg) , Gabriel Vasconcelos Pereira (University of Michigan) , Robert W. P. Glowacki (University of Michigan) , Sadie R. Gugel (University of Michigan) , Shaleni Singh (University of Michigan) , Dominic P. Byrne (University of Liverpool) , Nicholas A. Pudlo (University of Michigan) , James A. London (University of Liverpool) , Arnaud Basle (Newcastle University) , Mark Reihill (University College Dublin) , Stefan Oscarson (University College Dublin) , Patrick A. Eyers (University of Liverpool) , Mirjam Czjzek (Sorbonne Université, Univ Paris 06, CNRS, UMR 8227) , Gurvan Michel (Sorbonne Université, Univ Paris 06, CNRS, UMR 8227) , Tristan Barbeyron (Sorbonne Université, Univ Paris 06, CNRS, UMR 8227) , Edwin A. Yates (University of Liverpool) , Gunnar C. Hansson (University of Gothenburg) , Niclas G. Karlsson (University of Gothenburg) , Alan Cartmell (University of Liverpool) , Eric C. Martens (University of Michigan)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 105

State: Published (Approved)
Published: October 2021
Diamond Proposal Number(s): 18598

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. 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 and diseases such as inflammatory bowel disease.

Journal Keywords: Bacterial genetics; Bacteriology; Enzymes; Glycobiology

Diamond Keywords: Gut Microbiota; Bacteria; Enzymes; Inflammatory Bowel Disease

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: SOLEIL

Added On: 11/10/2021 09:26

Documents:
s41586-021-03967-5.pdf

Discipline Tags:

Non-Communicable Diseases Autoimmune Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)