Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood
(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.
(Less)
- author
- Jensen, Mathias ; Stenfelt, Linn LU ; Ricci Hagman, Jennifer LU ; Pichler, Michael Jakob ; Weikum, Julia ; Nielsen, Tine Sofie ; Hult, Annika LU ; Morth, Jens Preben ; Olsson, Martin L LU and Abou Hachem, Maher LU
- organization
- publishing date
- 2024-04-29
- 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}}, }