The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Human gut microbiome viewed across age and geography
Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., Magris, M., Hidalgo, G., Baldassano, R. N., Anokhin, A. P., et al. (2012) · Nature · doi:10.1038/nature11053 · Cited by 7,815
Wiederschain, G. Y. (2009) · Biochemistry (Moscow) · doi:10.1134/s0006297909090156 · Cited by 4,089
Varki, A. P., Cummings, R. D., Esko, J. D., Freeze, H. H., Stanley, P., Bertozzi, C. R., Hart, G. W., & Etzler, M. E. (1999) · Cited by 2,384
On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database
Apweiler, R. (1999) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(99)00165-8 · Cited by 1,857
Lactoferrin: structure, function and applications
González‐Chávez, S. A., Arévalo‐Gallegos, S., & Rascón-Cruz, Q. (2008) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2008.07.020 · Cited by 759
Establishment of the gut microbiota in Western infants
Adlerberth, I., & Wold, A. E. (2009) · Acta Paediatrica · doi:10.1111/j.1651-2227.2008.01060.x · Cited by 665
Raju, T. S., Briggs, J. B., Borge, S., & Jones, A. J. S. (2000) · Glycobiology · doi:10.1093/glycob/10.5.477 · Cited by 451
Cognition, reserve, and amyloid deposition in normal aging
Rentz, D. M., Locascio, J. J., Becker, J. A., Moran, E. K., Eng, E., Buckner, R. L., Sperling, R. A., & Johnson, K. A. (2009) · Annals of Neurology · doi:10.1002/ana.21904 · Cited by 420
Breast-v.formula-feeding: impacts on the digestive tract and immediate and long-term health effects
Le Huërou-Luron, I., Blat, S., & Boudry, G. (2010) · Nutrition Research Reviews · doi:10.1017/s0954422410000065 · Cited by 407
The integrated microbial genomes (IMG) system
Markowitz, V. M. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj024 · Cited by 381
Collin, M., & Olsén, A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.12.3046 · Cited by 367
Mitoulas, L. R., Kent, J. C., Cox, D. B., Owens, R. A., Sherriff, J. L., & Hartmann, P. E. (2002) · British Journal Of Nutrition · doi:10.1079/bjn2002579 · Cited by 321
Glycosylation profiling of immunoglobulin G (IgG) subclasses from human serum
Wuhrer, M., Stam, J. C., van de Geijn, F. E., Koeleman, C. A. M., Verrips, C. T., Dolhain, R. J. E. M., Hokke, C. H., & Deelder, A. M. (2007) · PROTEOMICS · doi:10.1002/pmic.200700289 · Cited by 269
Sela, D. A., Garrido, D. A., Lerno, L., Wu, S., Tan, K., Eom, H., Joachimiak, A., Lebrilla, C. B., & Mills, D. A. (2011) · Applied and Environmental Microbiology · doi:10.1128/aem.06762-11 · Cited by 259
Self-citationDetermination of N-Glycosylation Sites and Site Heterogeneity in Glycoproteins
An, H. J., Peavy, T. R., Hedrick, J. L., & Lebrilla, C. B. (2003) · Analytical Chemistry · doi:10.1021/ac034414x · Cited by 242
Self-citationGarrido, D. A., Kim, J., German, J. B., Raybould, H. E., & Mills, D. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017315 · Cited by 229
Self-citationMucin Degradation by Bifidobacterium Strains Isolated from the Human Intestinal Microbiota
Ruas‐Madiedo, P., Gueimonde, M., Fernández-García, M., Reyes‐Gavilán, C. G. D. L., & Margollés, A. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.02509-07 · Cited by 222
Trimble, R. B., & Tarentino, A. L. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)52343-7 · Cited by 207
Synstad, B., Gåseidnes, S., van Aalten, D. M. F., Vriend, G., Nielsen, J. E., & Eijsink, V. G. H. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03923.x · Cited by 186
Protein N-Glycosylation, Protein Folding, and Protein Quality Control
Roth, J., Zuber, C., Park, S., Jang, I., Lee, Y., Gaplovská-Kyselá, K., Fourn, V. L., Santimaria, R., Guhl, B., & Cho, J. W. (2010) · Molecules and Cells · doi:10.1007/s10059-010-0159-z · Cited by 183
Barboza, M., Pinzon, J., Wickramasinghe, S., Froehlich, J. W., Moeller, I., Smilowitz, J. T., Ruhaak, L. R., Huang, J., Lönnerdal, B. L., German, J. B., et al. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.015248 · Cited by 176
Self-citationFujita, K., Oura, F., Nagamine, N., Katayama, T., Hiratake, J., Sakata, K., Kumagai, H., & Yamamoto, K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506874200 · Cited by 175
BRINES, R., & BROCK, J. (1983) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(83)90317-3 · Cited by 152
Weber, A., Morse, M., & Gay, N. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403830200 · Cited by 149
A molecular basis for bifidobacterial enrichment in the infant gastrointestinal tract
Garrido, D., Barile, D., & Mills, D. A. (2012) · Advances in Nutrition · doi:10.3945/an.111.001586 · Cited by 149
Self-citationvan Berkel, P. H. C., Geerts, M., van Veen, H. A., Kooiman, P. M., Pieper, F. R., de Boer, H. A., & Nuijens, J. H. (1995) · Biochemical Journal · doi:10.1042/bj3120107 · Cited by 143
Picariello, G., Ferranti, P., Mamone, G., Roepstorff, P., & Addeo, F. (2008) · PROTEOMICS · doi:10.1002/pmic.200701057 · Cited by 141
LoCascio, R. G., Niñonuevo, M. R., Kronewitter, S. R., Freeman, S. L., German, J. B., Lebrilla, C. B., & Mills, D. A. (2008) · Microbial Biotechnology · doi:10.1111/j.1751-7915.2008.00072.x · Cited by 138
Self-citationZhang, G., Mills, D. A., & Block, D. E. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.01416-08 · Cited by 133
Self-citationvan Veen, H. A., Geerts, M., van Berkel, P. H. C., & Nuijens, J. H. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2003.03965.x · Cited by 132
Simultaneous and Extensive Site-specific N- and O-Glycosylation Analysis in Protein Mixtures
Nwosu, C. C., Seipert, R. R., Strum, J. S., Hua, S. S., An, H. J., Zivkovic, A. M., German, B. J., & Lebrilla, C. B. (2011) · Journal of Proteome Research · doi:10.1021/pr2001429 · Cited by 127
Self-citationStructural and Functional Analyses of the Human Toll-like Receptor 3
Sun, J., Duffy, K. E., Ranjith-Kumar, C. T., Xiong, J., Lamb, R. J., Santos, J., Hema, M., Cunningham, M., Holzenburg, A., Sarisky, R. T., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510442200 · Cited by 125
German, J. B., Dillard, C. J., & Ward, R. E. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200211000-00007 · Cited by 121
Self-citationSite-specific protein glycosylation analysis with glycan isomer differentiation
Hua, S. S., Nwosu, C. C., Strum, J. S., Seipert, R. R., An, H. J., Zivkovic, A. M., German, J. B., & Lebrilla, C. B. (2011) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-011-5109-x · Cited by 118
Self-citationSpecific binding of lactoferrin to brush-border membrane: ontogeny and effect of glycan chain
Davidson, L. A., & Lönnerdal, B. L. (1988) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1988.254.4.g580 · Cited by 116
Mathias, A., & Corthésy, B. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.209015 · Cited by 111
IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions
Collin, M., Shannon, O., & Björck, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711271105 · Cited by 110
Human IgG/FcγR Interactions Are Modulated by Streptococcal IgG Glycan Hydrolysis
Allhorn, M., Olin, A. I., Nimmerjahn, F., & Collin, M. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001413 · Cited by 101
Glycoprotein Expression in Human Milk during Lactation
Froehlich, J. W., Dodds, E. D., Barboza, M., McJimpsey, E. L., Seipert, R. R., Francis, J., An, H. J., Freeman, S. L., German, J. B., & Lebrilla, C. B. (2010) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf100112x · Cited by 97
Self-citationPetschow, B. W., TALBOTT, R. D., & Batema, R. P. (1999) · Journal of Medical Microbiology · doi:10.1099/00222615-48-6-541 · Cited by 94
The Nutritional Role of Breast‐Milk IgA and Lactoferrin
Prentice, A. M., Ewing, G., Roberts, S. B., Lucas, A., MacCARTHY, A., Jarjou, L., & Whitehead, R. G. (1987) · Acta Paediatrica · doi:10.1111/j.1651-2227.1987.tb10526.x · Cited by 92
Inverse Correlation between the Extent of N-Glycan Branching and Intercellular Adhesion in Epithelia
Vagin, O., Tokhtaeva, E., Yakubov, I., Shevchenko, E., & Sachs, G. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704713200 · Cited by 91
Trimble, R. B., & Maley, F. (1977) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(77)90512-5 · Cited by 87
Muramatsu, H., Tachikui, H., Ushida, H., Song, X., Qiu, Y., Yamamoto, S., & Muramatsu, T. (2001) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a002938 · Cited by 85
The long-term health effects of neonatal microbial flora
Conroy, M. E., Shi, H. N., & Walker, W. A. (2009) · Current Opinion in Allergy & Clinical Immunology · doi:10.1097/aci.0b013e32832b3f1d · Cited by 83
Renzi, F., Manfredi, P., Mally, M., Moes, S., Jenö, P., & Cornelis, G. R. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002118 · Cited by 79
Collin, M., & Fischetti, V. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402156200 · Cited by 76
Fathallah‐Shaykh, H. M. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.19 · Cited by 69
Yu, T., Guo, C., Wang, J., Hao, P., Sui, S., Chen, X., Zhang, R., Wang, P., Yu, G., Zhang, L., et al. (2010) · Glycobiology · doi:10.1093/glycob/cwq151 · Cited by 68
Enhanced Detection and Identification of Glycopeptides in Negative Ion Mode Mass Spectrometry
Nwosu, C. C., Strum, J. S., An, H. J., & Lebrilla, C. B. (2010) · Analytical Chemistry · doi:10.1021/ac101856r · Cited by 56
Self-citationMHCII glycosylation modulates Bacteroides fragilis carbohydrate antigen presentation
Ryan, S. O., Bonomo, J. A., Zhao, F., & Cobb, B. A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100508 · Cited by 53
Deguchi, K., Ito, H., Baba, T., Hirabayashi, A., Nakagawa, H., Fumoto, M., Hinou, H., & Nishimura, S. (2007) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.2885 · Cited by 46
Growth promotion and cell binding ability of bovine lactoferrin to Bifidobacterium longum
Rahman, M. M., Kim, W., Ito, T., Kumura, H., & Shimazaki, K. (2009) · Anaerobe · doi:10.1016/j.anaerobe.2009.01.003 · Cited by 43
Clowers, B. H., Dodds, E. D., Seipert, R. R., & Lebrilla, C. B. (2008) · Analytical Biochemistry · doi:10.1016/j.ab.2008.06.041 · Cited by 42
Self-citationStructure and Kinetics of a Monomeric Glucosamine 6-Phosphate Deaminase
Vincent, F., Davies, G. J., & Brannigan, J. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502131200 · Cited by 42
Roberts, G., Tarelli, E., Homer, K. A., Philpott‐Howard, J., & Beighton, D. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.4.882-890.2000 · Cited by 32
Pierce, A., Pamblanco, M., Strecker, G., Montreuil, J., Spik, G., DORLAND, L., van HALBEEK, H., & Vliegenthart, J. F. G. (1982) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1982.tb06694.x · Cited by 26
Yamamoto, S., Muramatsu, H., & Muramatsu, T. (2005) · Glycoconjugate Journal · doi:10.1007/s10719-005-0847-7 · Cited by 18
Functional and structural characterisation of human colostrum free secretory component
Almogren, A., Bonner, A., Perkins, S. J., & Kerr, M. A. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2008.12.022 · Cited by 15
Classic Studies of Mammary Development and Milk Secretion: 1945 – 1980
Neville, M. C. (2009) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-009-9151-7 · Cited by 14
Distribution of endo-β-N-acetylglucosaminidase amongst enterococci
ROBERTS, G. J., Homer, K. A., Tarelli, E., Philpott‐Howard, J., Devriese, L. A., & Beighton, D. (2001) · Journal of Medical Microbiology · doi:10.1099/0022-1317-50-7-620 · Cited by 13
Cited by
Sorted by citations
Carbohydrate metabolism in Bifidobacteria
Pokusaeva, K., Fitzgerald, G. F., & van Sinderen, D. (2011) · Genes & Nutrition · doi:10.1007/s12263-010-0206-6 · Cited by 890
Probiotics, Prebiotics and Immunomodulation of Gut Mucosal Defences: Homeostasis and Immunopathology
Hardy, H., Harris, J., Lyon, E., Beal, J., & Foey, A. (2013) · Nutrients · doi:10.3390/nu5061869 · Cited by 564
Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut
Underwood, M. A., German, J. B., Lebrilla, C. B., & Mills, D. A. (2015) · Pediatric Research · doi:10.1038/pr.2014.156 · Cited by 439
Self-citationBreast milk oligosaccharides: structure-function relationships in the neonate
Smilowitz, J. T., Lebrilla, C. B., Mills, D. A., German, J. B., & Freeman, S. L. (2014) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071813-105721 · Cited by 410
Self-citationThe Human Gut Microbiome and Body Metabolism: Implications for Obesity and Diabetes
Devaraj, S., Hemarajata, P., & Versalovic, J. (2013) · Clinical Chemistry · doi:10.1373/clinchem.2012.187617 · Cited by 321
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
