Identification of Allobaculum mucolyticum as a novel human intestinal mucin degrader

Guus H van Muijlwijk, Guido van Mierlo, Pascal W T C Jansen, Michiel Vermeulen, Nancy M C Bleumink-Pluym, Noah W Palm, Jos P M van Putten, Marcel R de Zoete

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The human gut microbiota plays a central role in intestinal health and disease. Yet, many of its bacterial constituents are functionally still largely unexplored. A crucial prerequisite for bacterial survival and proliferation is the creation and/or exploitation of an own niche. For many bacterial species that are linked to human disease, the inner mucus layer was found to be an important niche. Allobaculum mucolyticum is a newly identified, IBD-associated species that is thought be closely associated with the host epithelium. To explore how this bacterium is able to effectively colonize this niche, we screened its genome for factors that may contribute to mucosal colonization. Up to 60 genes encoding putative Carbohydrate Active Enzymes (CAZymes) were identified in the genome of A. mucolyticum. Mass spectrometry revealed 49 CAZymes of which 26 were significantly enriched in its secretome. Functional assays demonstrated the presence of CAZyme activity in A. mucolyticum conditioned medium, degradation of human mucin O-glycans, and utilization of liberated non-terminal monosaccharides for bacterial growth. The results support a model in which sialidases and fucosidases remove terminal O-glycan sugars enabling subsequent degradation and utilization of carbohydrates for A. mucolyticum growth. A. mucolyticum CAZyme secretion may thus facilitate bacterial colonization and degradation of the mucus layer and may pose an interesting target for future therapeutic intervention.

Original languageEnglish
Article number1966278
Pages (from-to)1-18
JournalGut Microbes
Volume13
Issue number1
DOIs
Publication statusPublished - 31 Aug 2021

Bibliographical note

Funding Information:
M.R.d.Z. was supported by a VIDI grant from the Netherlands Organization for Scientific Research (NWO, grant 91715377) and the Utrecht Exposome Hub of Utrecht Life Sciences (www.uu.nl/exposome), funded by the Executive Board of Utrecht University. We would like to kindly thank Dr. Karin Strijbis for providing the anti-human MUC2 rabbit serum. We would like to kindly thank Dr. Yvette Luijkx and Dr. Tom Wennekes for providing the activity-based probe and advice on experimental setup.

Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • Allobaculum mucolyticum
  • cazymes
  • glycosidase
  • intestinal mucin
  • microbiota
  • mucin degradation
  • mucin o-glycans
  • pathobiont
  • proteome

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