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Endo-β-N-acetylglucosaminidases from Infant Gut-associated Bifidobacteria Release Complex N-glycans from Human Milk Glycoproteins
Open accessAbstract
Breastfeeding is one of the main factors guiding the composition of the infant gut microbiota in the first months of life. This process is shaped in part by the high amounts of human milk oligosaccharides that serve as a carbon source for saccharolytic bacteria such as Bifidobacterium species. Infant-borne bifidobacteria have developed various molecular strategies for utilizing these oligosaccharides as a carbon source. We hypothesized that these species also interact with N-glycans found in host glycoproteins that are structurally similar to free oligosaccharides in human milk. Endo-β-N-acetylglucosaminidases were identified in certain isolates of Bifidobacterium longum subsp. longum, B. longum subsp. infantis, and Bifidobacterium breve, and their presence correlated with the ability of these strains to deglycosylate glycoproteins. An endoglycosidase from B. infantis ATCC 15697, EndoBI-1, was active toward all major types of N-linked glycans found in glycosylated proteins. Its activity was not affected by core fucosylation or extensive fucosylation, antenna number, or sialylation, releasing several N-glycans from human lactoferrin and immunoglobulins A and G. Extensive N-deglycosylation of whole breast milk was also observed after coincubation with this enzyme. Mutation of the active site of EndoBI-1 did not abolish binding to N-glycosylated proteins, and this mutant specifically recognized Man(3)GlcNAc(2)(α1-6Fuc), the core structure of human N-glycans. EndoBI-1 is constitutively expressed in B. infantis, and incubation of the bacterium with human or bovine lactoferrin led to the induction of genes associated to import and consumption of human milk oligosaccharides, suggesting linked regulatory mechanisms among these glycans. This work reveals an unprecedented interaction of bifidobacteria with host N-glycans and describes a novel endoglycosidase with broad specificity on diverse N-glycan types, potentially a useful tool for glycoproteomics studies.
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“However, B. infantis is able to produce extracellular glycosidases that allow it to cleave and consume these glycan moieties [45, 92].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [45]
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Metadata
- Authors
- Garrido, D., Nwosu, C., Ruiz-Moyano, S., Aldredge, D., German, J. B., Lebrilla, C. B., & Mills, D. A.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Mills, David A.
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 11
- Issue
- 9
- Pages
- 775-785
- ISSN
- 1535-9476 (ISSN-L)
- PMC
- PMC3434770
- OpenAlex
- W2097356400
- Cited by
- 150
- References
- 61
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 6 · 2022: 14 · 2021: 12 · 2020: 18 · 2019: 9 · 2018: 13 · 2017: 6 · 2016: 8 · 2015: 11 · 2014: 12 · 2013: 12 · 2012: 2
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular & Cellular Proteomics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Complementary and Integrative Health (R01AT007079)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065122, R01HD061923)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
- Keywords
- endo-beta-N-acetylglucosaminidase, Bifidobacterium, Bifidobacterium infantis, human milk oligosaccharides, N-glycans, lactoferrin, immunoglobulins, host-microbe interactions, infant gut microbiota, core fucosylation, sialylation, active site mutations, gene expression regulation
- MeSH terms
- Bifidobacterium, Glycoproteins, Humans, Infant, Infant, Newborn, Lactoferrin, Milk, Human, Polysaccharides, Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase, Gastrointestinal Tract, Metagenome
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