IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48802-3.html
   My bibliography  Save this article

Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate

Author

Listed:
  • Diego E. Sastre

    (Emory University School of Medicine)

  • Nazneen Sultana

    (Emory University School of Medicine
    National Institute of Dental and Craniofacial Research (NIDCR/NIH))

  • Marcos V. A. S. Navarro

    (University of São Paulo
    Cornell University)

  • Maros Huliciak

    (Emory University School of Medicine)

  • Jonathan Du

    (Emory University School of Medicine
    The University of Sydney)

  • Javier O. Cifuente

    (University of the Basque Country)

  • Maria Flowers

    (Emory University School of Medicine)

  • Xu Liu

    (Emory University School of Medicine)

  • Pete Lollar

    (Emory University School of Medicine)

  • Beatriz Trastoy

    (Biobizkaia Health Research Institute
    Basque Foundation for Science)

  • Marcelo E. Guerin

    (Tower R)

  • Eric J. Sundberg

    (Emory University School of Medicine)

Abstract

Bacteroidales (syn. Bacteroidetes) are prominent members of the human gastrointestinal ecosystem mainly due to their efficient glycan-degrading machinery, organized into gene clusters known as polysaccharide utilization loci (PULs). A single PUL was reported for catabolism of high-mannose (HM) N-glycan glyco-polypeptides in the gut symbiont Bacteroides thetaiotaomicron, encoding a surface endo-β-N-acetylglucosaminidase (ENGase), BT3987. Here, we discover an ENGase from the GH18 family in B. thetaiotaomicron, BT1285, encoded in a distinct PUL with its own repertoire of proteins for catabolism of the same HM N-glycan substrate as that of BT3987. We employ X-ray crystallography, electron microscopy, mass spectrometry-based activity measurements, alanine scanning mutagenesis and a broad range of biophysical methods to comprehensively define the molecular mechanism by which BT1285 recognizes and hydrolyzes HM N-glycans, revealing that the stabilities and activities of BT1285 and BT3987 were optimal in markedly different conditions. BT1285 exhibits significantly higher affinity and faster hydrolysis of poorly accessible HM N-glycans than does BT3987. We also find that two HM-processing endoglycosidases from the human gut-resident Alistipes finegoldii display condition-specific functional properties. Altogether, our data suggest that human gut microbes employ evolutionary strategies to express distinct ENGases in order to optimally metabolize the same N-glycan substrate in the gastroinstestinal tract.

Suggested Citation

  • Diego E. Sastre & Nazneen Sultana & Marcos V. A. S. Navarro & Maros Huliciak & Jonathan Du & Javier O. Cifuente & Maria Flowers & Xu Liu & Pete Lollar & Beatriz Trastoy & Marcelo E. Guerin & Eric J. S, 2024. "Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48802-3
    DOI: 10.1038/s41467-024-48802-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48802-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48802-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Fiona Cuskin & Elisabeth C. Lowe & Max J. Temple & Yanping Zhu & Elizabeth A. Cameron & Nicholas A. Pudlo & Nathan T. Porter & Karthik Urs & Andrew J. Thompson & Alan Cartmell & Artur Rogowski & Brian, 2015. "Correction: Corrigendum: Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism," Nature, Nature, vol. 520(7547), pages 388-388, April.
    2. Sarah E. Williams & Maxence Noel & Sylvain Lehoux & Murat Cetinbas & Ramnik J. Xavier & Ruslan I. Sadreyev & Edward M. Scolnick & Jordan W. Smoller & Richard D. Cummings & Robert G. Mealer, 2022. "Mammalian brain glycoproteins exhibit diminished glycan complexity compared to other tissues," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Tadashi Takeuchi & Tetsuya Kubota & Yumiko Nakanishi & Hiroshi Tsugawa & Wataru Suda & Andrew Tae-Jun Kwon & Junshi Yazaki & Kazutaka Ikeda & Shino Nemoto & Yoshiki Mochizuki & Toshimori Kitami & Kats, 2023. "Gut microbial carbohydrate metabolism contributes to insulin resistance," Nature, Nature, vol. 621(7978), pages 389-395, September.
    4. Didier Ndeh & Artur Rogowski & Alan Cartmell & Ana S. Luis & Arnaud Baslé & Joseph Gray & Immacolata Venditto & Jonathon Briggs & Xiaoyang Zhang & Aurore Labourel & Nicolas Terrapon & Fanny Buffetto &, 2017. "Correction: Corrigendum: Complex pectin metabolism by gut bacteria reveals novel catalytic functions," Nature, Nature, vol. 548(7669), pages 612-612, August.
    5. Didier Ndeh & Artur Rogowski & Alan Cartmell & Ana S. Luis & Arnaud Baslé & Joseph Gray & Immacolata Venditto & Jonathon Briggs & Xiaoyang Zhang & Aurore Labourel & Nicolas Terrapon & Fanny Buffetto &, 2017. "Complex pectin metabolism by gut bacteria reveals novel catalytic functions," Nature, Nature, vol. 544(7648), pages 65-70, April.
    6. Beatriz Trastoy & Jonathan J. Du & Erik H. Klontz & Chao Li & Javier O. Cifuente & Lai-Xi Wang & Eric J. Sundberg & Marcelo E. Guerin, 2020. "Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    7. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    8. Declan A. Gray & Joshua B. R. White & Abraham O. Oluwole & Parthasarathi Rath & Amy J. Glenwright & Adam Mazur & Michael Zahn & Arnaud Baslé & Carl Morland & Sasha L. Evans & Alan Cartmell & Carol V. , 2021. "Insights into SusCD-mediated glycan import by a prominent gut symbiont," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    9. Manimozhiyan Arumugam & Jeroen Raes & Eric Pelletier & Denis Le Paslier & Takuji Yamada & Daniel R. Mende & Gabriel R. Fernandes & Julien Tap & Thomas Bruls & Jean-Michel Batto & Marcelo Bertalan & Na, 2011. "Enterotypes of the human gut microbiome," Nature, Nature, vol. 473(7346), pages 174-180, May.
    10. Manimozhiyan Arumugam & Jeroen Raes & Eric Pelletier & Denis Le Paslier & Takuji Yamada & Daniel R. Mende & Gabriel R. Fernandes & Julien Tap & Thomas Bruls & Jean-Michel Batto & Marcelo Bertalan & Na, 2011. "Erratum: Enterotypes of the human gut microbiome," Nature, Nature, vol. 474(7353), pages 666-666, June.
    11. Fiona Cuskin & Elisabeth C. Lowe & Max J. Temple & Yanping Zhu & Elizabeth A. Cameron & Nicholas A. Pudlo & Nathan T. Porter & Karthik Urs & Andrew J. Thompson & Alan Cartmell & Artur Rogowski & Brian, 2015. "Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism," Nature, Nature, vol. 517(7533), pages 165-169, January.
    12. Beatriz Trastoy & Jonathan J. Du & Javier O. Cifuente & Lorena Rudolph & Mikel García-Alija & Erik H. Klontz & Daniel Deredge & Nazneen Sultana & Chau G. Huynh & Maria W. Flowers & Chao Li & Diego E. , 2023. "Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jennifer L. Modesto & Victoria H. Pearce & Guy E. Townsend, 2023. "Harnessing gut microbes for glycan detection and quantification," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Hao-Tian Wang & Zi-Long Wang & Kuan Chen & Ming-Ju Yao & Meng Zhang & Rong-Shen Wang & Jia-He Zhang & Hans Ågren & Fu-Dong Li & Junhao Li & Xue Qiao & Min Ye, 2023. "Insights into the missing apiosylation step in flavonoid apiosides biosynthesis of Leguminosae plants," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Antonella Gagliardi & Valentina Totino & Fatima Cacciotti & Valerio Iebba & Bruna Neroni & Giulia Bonfiglio & Maria Trancassini & Claudio Passariello & Fabrizio Pantanella & Serena Schippa, 2018. "Rebuilding the Gut Microbiota Ecosystem," IJERPH, MDPI, vol. 15(8), pages 1-24, August.
    4. Yonggan Sun & Qixing Nie & Shanshan Zhang & Huijun He & Sheng Zuo & Chunhua Chen & Jingrui Yang & Haihong Chen & Jielun Hu & Song Li & Jiaobo Cheng & Baojie Zhang & Zhitian Zheng & Shijie Pan & Ping H, 2023. "Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Aaron Franklin & Vivian C. Salgueiro & Abigail J. Layton & Rudi Sullivan & Todd Mize & Lucía Vázquez-Iniesta & Samuel T. Benedict & Sudagar S. Gurcha & Itxaso Anso & Gurdyal S. Besra & Manuel Banzhaf , 2024. "The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. M. C. Rühlemann & C. Bang & J. F. Gogarten & B. M. Hermes & M. Groussin & S. Waschina & M. Poyet & M. Ulrich & C. Akoua-Koffi & T. Deschner & J. J. Muyembe-Tamfum & M. M. Robbins & M. Surbeck & R. M. , 2024. "Functional host-specific adaptation of the intestinal microbiome in hominids," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Emidio Scarpellini & Emanuele Rinninella & Martina Basilico & Esther Colomier & Carlo Rasetti & Tiziana Larussa & Pierangelo Santori & Ludovico Abenavoli, 2021. "From Pre- and Probiotics to Post-Biotics: A Narrative Review," IJERPH, MDPI, vol. 19(1), pages 1-14, December.
    8. Stefan Dyksma & Michael Pester, 2023. "Oxygen respiration and polysaccharide degradation by a sulfate-reducing acidobacterium," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Omar Al-Jourani & Samuel T. Benedict & Jennifer Ross & Abigail J. Layton & Phillip Peet & Victoria M. Marando & Nicholas P. Bailey & Tiaan Heunis & Joseph Manion & Francesca Mensitieri & Aaron Frankli, 2023. "Identification of d-arabinan-degrading enzymes in mycobacteria," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Zhiguang Qiu & Li Yuan & Chun-Ang Lian & Bin Lin & Jie Chen & Rong Mu & Xuejiao Qiao & Liyu Zhang & Zheng Xu & Lu Fan & Yunzeng Zhang & Shanquan Wang & Junyi Li & Huiluo Cao & Bing Li & Baowei Chen & , 2024. "BASALT refines binning from metagenomic data and increases resolution of genome-resolved metagenomic analysis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Elio L Herzog & Melania Wäfler & Irene Keller & Sebastian Wolf & Martin S Zinkernagel & Denise C Zysset-Burri, 2021. "The importance of age in compositional and functional profiling of the human intestinal microbiome," PLOS ONE, Public Library of Science, vol. 16(10), pages 1-13, October.
    12. María Ángeles Rivas & Rocío Casquete & Alberto Martín & María de Guía Córdoba & Emilio Aranda & María José Benito, 2021. "Strategies to Increase the Biological and Biotechnological Value of Polysaccharides from Agricultural Waste for Application in Healthy Nutrition," IJERPH, MDPI, vol. 18(11), pages 1-19, June.
    13. Oliver Aasmets & Kertu Liis Krigul & Kreete Lüll & Andres Metspalu & Elin Org, 2022. "Gut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Julien Tap & Franck Lejzerowicz & Aurélie Cotillard & Matthieu Pichaud & Daniel McDonald & Se Jin Song & Rob Knight & Patrick Veiga & Muriel Derrien, 2023. "Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    15. Lharbi Dridi & Fernando Altamura & Emmanuel Gonzalez & Olivia Lui & Ryszard Kubinski & Reilly Pidgeon & Adrian Montagut & Jasmine Chong & Jianguo Xia & Corinne F. Maurice & Bastien Castagner, 2023. "Identifying glycan consumers in human gut microbiota samples using metabolic labeling coupled with fluorescence-activated cell sorting," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    16. Kihyun Lee & Sebastien Raguideau & Kimmo Sirén & Francesco Asnicar & Fabio Cumbo & Falk Hildebrand & Nicola Segata & Chang-Jun Cha & Christopher Quince, 2023. "Population-level impacts of antibiotic usage on the human gut microbiome," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    17. Roger S. Fujioka & Helena M. Solo-Gabriele & Muruleedhara N. Byappanahalli & Marek Kirs, 2015. "U.S. Recreational Water Quality Criteria: A Vision for the Future," IJERPH, MDPI, vol. 12(7), pages 1-25, July.
    18. Feng Tong & Teng Wang & Na L. Gao & Ziying Liu & Kuiqing Cui & Yiqian Duan & Sicheng Wu & Yuhong Luo & Zhipeng Li & Chengjian Yang & Yixue Xu & Bo Lin & Liguo Yang & Alfredo Pauciullo & Deshun Shi & G, 2022. "The microbiome of the buffalo digestive tract," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Mendler, Isabella-Hilda & Drossel, Barbara & Hütt, Marc-Thorsten, 2024. "Microbiome abundance patterns as attractors and the implications for the inference of microbial interaction networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 639(C).
    20. Gertrude Ecklu-Mensah & Candice Choo-Kang & Maria Gjerstad Maseng & Sonya Donato & Pascal Bovet & Bharathi Viswanathan & Kweku Bedu-Addo & Jacob Plange-Rhule & Prince Oti Boateng & Terrence E. Forrest, 2023. "Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48802-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.