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Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood

Jensen, Mathias ; Stenfelt, Linn LU orcid ; Ricci Hagman, Jennifer LU ; Pichler, Michael Jakob ; Weikum, Julia ; Nielsen, Tine Sofie ; Hult, Annika LU ; Morth, Jens Preben ; Olsson, Martin L LU orcid and Abou Hachem, Maher LU (2024) In Nature Microbiology
Abstract

Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with... (More)

Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.

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organization
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type
Contribution to journal
publication status
epub
subject
in
Nature Microbiology
publisher
Springer Nature
external identifiers
  • pmid:38684911
  • scopus:85191742379
ISSN
2058-5276
DOI
10.1038/s41564-024-01663-4
language
English
LU publication?
yes
id
20d53ecc-fca1-4ffe-ae4a-a70e72533a54
date added to LUP
2024-04-30 12:56:35
date last changed
2024-05-21 14:19:57
@article{20d53ecc-fca1-4ffe-ae4a-a70e72533a54,
  abstract     = {{<p>Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.</p>}},
  author       = {{Jensen, Mathias and Stenfelt, Linn and Ricci Hagman, Jennifer and Pichler, Michael Jakob and Weikum, Julia and Nielsen, Tine Sofie and Hult, Annika and Morth, Jens Preben and Olsson, Martin L and Abou Hachem, Maher}},
  issn         = {{2058-5276}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Springer Nature}},
  series       = {{Nature Microbiology}},
  title        = {{Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood}},
  url          = {{http://dx.doi.org/10.1038/s41564-024-01663-4}},
  doi          = {{10.1038/s41564-024-01663-4}},
  year         = {{2024}},
}