Unique adaptations in sulfatases underpin colonic mucin degradation by Akkermansia muciniphila
Excessive foraging of colonic mucin glycans by gut bacteria is associated with diseases such as inflammatory bowel disease. Although Akkermansia muciniphila is an important mucin degrader, the role of carbohydrate sulfatases that facilitate digestion of these heavily sulfated glycans remains unclear. Combining in vitro digestion assays, proteomics and structural biology, we show that A. muciniphila sulfatases, such as Amuc1755 and Amuc0953, have rare adaptations targeted towards known sulfated mucin structures. They show larger degrees of modularity, including a previously unknown mucin-binding domain. When grown on colonic mucin substrates, glycoproteins of reduced size were important for the growth of A. muciniphila. Further mutational analysis and localization studies revealed that desulfation of N-acetyl-D-glucosamine was periplasmic, while desulfation of D-galactose occurred extracellularly and in the periplasm. These data improve our understanding of contexts for the positive health correlations of A. muciniphila while metabolizing colonic mucin as its sole carbon source.
Authors
- Charles W.E. Tomlinson (ORCID: https://orcid.org/0000-0002-1845-6028)
- Mihai Oltean (ORCID: https://orcid.org/0000-0003-3783-5207)
- Christoph G. Baumann (ORCID: https://orcid.org/0000-0002-8818-972X)
- Alan Cartmell (ORCID: https://orcid.org/0000-0002-5512-249X)
- Ana S. Luís (ORCID: https://orcid.org/0000-0002-5086-7353)
- Reyme Herman (ORCID: https://orcid.org/0000-0002-6620-3981)
- Eric C. Martens (ORCID: https://orcid.org/0000-0001-6681-2990)
- Zak McIver (ORCID: https://orcid.org/0000-0002-4352-9049)
- Debajit Dey (ORCID: https://orcid.org/0000-0001-8289-7904)
- Gareth S. A. Wright (ORCID: https://orcid.org/0000-0002-3756-9634)
- Lauren Davey (ORCID: https://orcid.org/0000-0002-9541-485X)
- Mirjam Czjzek (ORCID: https://orcid.org/0000-0002-7483-2841)
- Chunsheng Jin (ORCID: https://orcid.org/0000-0002-0229-102X)
- Grete Raba (ORCID: https://orcid.org/0000-0002-7764-3878)
- Sjoerd van der Post (ORCID: https://orcid.org/0000-0002-7965-5311)
- Alexander Case
- E D Yates
- Naba Salman
- Dominic P. Byrne (ORCID: https://orcid.org/0000-0001-5197-345X)
- Daniel J. Rigden
- Marcus Nilsson
- Matthew Davy
- Sadie R. Schaus
- Adam Simpkin
Institutions
- University of Essex (GB)
- Tallinn University of Technology (EE)
- Centre National de la Recherche Scientifique (FR)
- University of Liverpool (GB)
- University of Victoria (CA)
- University of Michigan (US)
- Science for Life Laboratory (SE)
- Sahlgrenska University Hospital (SE)
- Station Biologique de Roscoff (FR)
- Sorbonne Université (FR)
- Laboratoire de Biologie Intégrative des Modèles Marins (FR)
- University of York (GB)
- University of Gothenburg (SE)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2026-07-27
- DOI
- https://doi.org/10.1038/s41564-026-02424-1
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00