Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown
Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown
Abstract The human gut microbiota (HGM) are closely associated with health, development and disease. The thick intestinal mucus layer, especially in the colon, is the key barrier between the contents of the lumen and the epithelial cells, providing protection against infiltration by the microbiota as well potential pathogens. The upper layer of the colonic mucus is a niche for a subset of the microbiota which utilise the mucin glycoproteins as a nutrient source and mucin grazing by the microbiota appears to play a key role in maintaining barrier function as well as community stability. Despite the importance of mucin breakdown for gut health, the mechanisms by which gut bacteria access this complex glycoprotein are not well understood. The current model for mucin degradation involves exclusively exo-acting glycosidases that sequentially trim monosaccharides from the termini of the glycan chains to eventually allow access to the mucin peptide backbone by proteases. However, this model is in direct contrast to the Sus paradigm of glycan breakdown used by the Bacteroidetes which involves extracellular cleavage of glycans by surface located endo-acting enzymes prior to import of the oligosaccharide products. Here we describe the discovery and characterisation of endo-acting family 16 glycoside hydrolases (GH16s) from prominent mucin degrading gut bacteria that specifically target the oligosaccharide side chains of intestinal mucins from both animals and humans. These endo-acting O-glycanases display β1,4-glactosidase activity and in several cases are surface located indicating they are involved in the initial step in mucin breakdown. The data suggest a new paradigm for mucin breakdown by the microbiota and the endo-mucinases provide a potential tool to explore changes that occur in mucin structure in intestinal disorders such as inflammatory bowel disease and colon cancer.
Cooke Katie、Glowacki Robert、Spencer Daniel I. R.、Liberato Marcelo V.、Doona Mary、Needham Stephanie、Berrington Janet E.、Pearson Jeffery P.、Martens Eric C.、Linhardt Robert J.、Wuhrer Manfred、Stewart Christopher J.、Bolam David N.、Urbanowicz Paulina A.、Crouch Lucy I.、Brady Richard R.、Zhang Fuming、Chater Peter、Lamb Christopher A.、Madunic Katarina、Basl¨| Arnaud
Institute of Cellular Medicine, Newcastle UniversityDepartment of Microbiology and Immunology, University of Michigan Medical SchoolLudger Ltd, Culham Science CentreUniversidade de Sorocaba, Programa de Processos Tecnol¨?gicos e AmbientaisDepartment of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation TrustDepartment of Histopathology, Newcastle upon Tyne Hospitals NHS Foundation TrustNewcastle Neonatal Service, Royal Victoria InfirmaryInstitute of Cell and Molecular Biosciences, Newcastle UniversityDepartment of Microbiology and Immunology, University of Michigan Medical SchoolDepartment of Chemistry and Chemical Biology, Centre for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic InstituteCentre for Proteomics and Metabolomics, Leiden University Medical CentreInstitute of Cellular Medicine, Newcastle UniversityInstitute of Cell and Molecular Biosciences, Newcastle UniversityLudger Ltd, Culham Science CentreInstitute of Cell and Molecular Biosciences, Newcastle UniversityDepartment of Colorectal Surgery, Newcastle upon Tyne Hospitals NHS Foundation TrustDepartment of Chemistry and Chemical Biology, Centre for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic InstituteInstitute of Cell and Molecular Biosciences, Newcastle UniversityDepartment of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation TrustCentre for Proteomics and Metabolomics, Leiden University Medical CentreInstitute of Cell and Molecular Biosciences, Newcastle University
微生物学分子生物学生理学
Cooke Katie,Glowacki Robert,Spencer Daniel I. R.,Liberato Marcelo V.,Doona Mary,Needham Stephanie,Berrington Janet E.,Pearson Jeffery P.,Martens Eric C.,Linhardt Robert J.,Wuhrer Manfred,Stewart Christopher J.,Bolam David N.,Urbanowicz Paulina A.,Crouch Lucy I.,Brady Richard R.,Zhang Fuming,Chater Peter,Lamb Christopher A.,Madunic Katarina,Basl¨| Arnaud.Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown[EB/OL].(2025-03-28)[2025-05-14].https://www.biorxiv.org/content/10.1101/835843.点此复制
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