Unique adaptations in sulfatases underpin colonic mucin degradation by Akkermansia muciniphila

Abstract

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.

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Item Type:	Article
Authors/Creators:	Dey, D. https://orcid.org/0000-0001-8289-7904 Salman, N.D. Tomlinson, C.W.E. Jin, C. Raba, G. Schaus, S.R. Nilsson, M. McIver, Z. Herman, R. Simpkin, A. Davy, M. Rigden, D.J. Czjzek, M. Byrne, D.P. Oltean, M. Case, A. Baumann, C.G. Wright, G.S.A. van der Post, S. Yates, E.A. Martens, E.C. Davey, L. Luis, A.S. Cartmell, A.
Copyright, Publisher and Additional Information:	© The Author(s) 2026, modified publication 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 10 June 2026 Published (online): 27 July 2026 Published: September 2026
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Biological Chemistry (Leeds)
Date Deposited:	28 Oct 2026 17:13
Last Modified:	28 Oct 2026 17:13
Status:	Published
Publisher:	Nature Research
Identification Number:	10.1038/s41564-026-02424-1
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:246852

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Unique adaptations in sulfatases underpin colonic mucin degradation by Akkermansia muciniphila

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