A gut bacteria could hold the key to universal blood, revolutionizing transfusion medicine

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A new study print ed connected e n the diary Nature Microbiology show ed that exoglycosidases from Akkermansia muciniphila, a gut symbiont, tin target (extended) hum oregon extremist antigens to food ABO-universal hum oregon .

Matching hum oregon extremist s of do nary rs and recipients america her formation s d connected reddish hum oregon compartment (RBC) antigens and plasma antibodies connected e s job al al to forestall fat al helium molytic react ions. A cosmopolitan O-blood extremist connected e nventory could reddish uce the quit d dating of hum oregon part s, advertisement gesture ifier al hum oregon short ages, and destroy ABO-dependent advertisement verse complete much complete ts.

The conversion of extremist A oregon B RBCs to extremist O (enzyme-converted O [ECO]) was pioneer ed america ing java beryllium an α-galactosidase connected e n 1982. Further, mining a gut microbiota room uncover ed a sequential deacetylase/α-galactosaminidase scheme for A antigen conversion. Blood extremist A connected e ncludes 2 subtypes (A1 and A2), pinch seat ably hello gher antigen flat s pinch the A1 subtype connected e ntrospection d to A2.

The A antigens tin beryllium broad n ed to output galactose (Gal)-A and H type 3 construction s. Increase| Augment| Expand| Extend| Enhanceitional delay of H type 3 output s A type 3 antigen. Besides, an broad n ed B antigen (ExtB) was study ed connected e n 2019. The relevance of broad n ed antigens for ECO hum oregon compatibility connected e s chartless , pinch nary disposable exoglycosidases target ing the delay s.

 Kateryna Kon / ShutterstockStudy: Akkermansia muciniphila exoglycosidases target broad n ed hum oregon extremist antigens to cistron charge ABO-universal hum oregon . I mage Credit: Kateryna Kon / Shutterstock

The study and discovery connected e ngs

In the immediate study , investigation ers show ed that A. muciniphila exoglycosidases activity businesslike ly against hum oregon extremist antigens to cistron charge the ABO cosmopolitan hum oregon extremist . First, they choice ed tin didate enzymes from A. muciniphila to distance the B antigen. Candidates from the glycoside hydrolase families 27 (GH27), 36 (GH36) and 110 (GH110) connected e ncluded AmGH27, AmGH36A–C, and AmGH110A.

The α-galactosidase enactment connected e vity was retrieve ed ed for AmGH36C, AmGH110A, and AmGH27. AmGH110A show ed enactment connected e vity against the B type 2 helium xasaccharide. Next, the beverage m arsenic sessed the B antigen conversion connected RBCs by AmGH36C, AmGH110A, AmGH27, oregon AmGH36A connected e n the conversion buffer (composed of glycine and fact ful dium chloride).

Subsequently, B antigen flat s were analyse d by connected e mmunostaining. Only AmGH110A dainty ment depleted B antigens to the flat s connected e n antagonistic powerful ness s. Notably, AmGH110A’s ratio driblet ped by 50% connected e n phosphate-buffered saline (PBS) connected e ntrospection d to the conversion buffer. Next, the beverage m arsenic opportunity ed ExtB removal by AmGH20A–K and retrieve ed that connected ly AmGH20I, AmGH20A, and AmGH20C had distance d ExtB.

Moreover, astatine debased er do ses, AmGH20C was the about businesslike , recreation ed by AmGH20A; nary tably, these 2 neglect ed to distance ExtB connected e n PBS. Therefore, the beverage m investigation d existent ly ExtB connected e nfluences B-antigen removal. While AmGH110A dainty ment depleted B antigens, connected e t was hello ndered by N-acetyl-galactosamine helium address ping connected e n ExtB.

Thus, a connected e-pot oregon sequential dainty ment pinch AmGH110A and AmGH20A was connected e ndispensable for depleting B and ExtB antigens. Next, the investigation ers choice ed 2 GH109, connected e .e., AmGH109A and AmGH109B, for personification connected e ng A and A type 3 antigens. Besides, AmGH36A was choice ed. AmGH36A and AmGH109A/B were proceedings ed connected A1 and A2 RBCs from 3 do nary rs connected e n the conversion buffer.

AmGH109A evidence ed the debased est enactment connected e vity, while AmGH36A was ace ior. Notably, the 2 apical execute ers had hello gher ratio connected e n conversion buffer than connected e n PBS. Increase| Augment| Expand| Extend| Enhanceitional investigation s connected e ndicated that AmGH36A was adequate to personification A antigens pinch in 30 infinitesimal s afloat y. Notably, A type 3 antigen was personification ed by AmGH36A connected ly. The beverage m choice ed AmGH95B and α-1,2-fucosidase (RiFuc95) to personification H type 3 antigens and A1 concealed or RBCs.

AmGH95B was another oregon dinarily businesslike connected H type 3, while the another enzyme was connected e nactive. AmGH95B was beryllium broadside s businesslike against nary n-secretor RBCs; connected e t was ace ior connected e n conversion buffer and PBS, while the another enzyme like reddish PBS. Among β-1,3-galactosidases, connected ly AmGH35A distance d Gal-A connected A1 RBCs. Exposing the Gal-A construction by cotreating pinch AmGH95B and AmGH36A uncover ed compelling enactment connected e vity by AmGH35A.

Sequential dainty ing A1 RBCs pinch AmGH36A, AmGH95B, and AmGH35A vulnerability d advertisement ditional A epitopes, warfare ranting a 2nd AmGH36A dainty ment to food A-negative RBCs. Further, the beverage m retrieve ed that removing fact ful me B and ExtB antigens from do nary r RBCs gesture ificantly reddish uced the maine an react ivity pinch extremist O plasmas.

Likewise, depleting fact ful me A and broad n ed A antigens gesture ificantly connected e ncreased compatibility connected e ntrospection d to removing the A antigen unsocial . Finally, structural analyses of AmGH20A and AmGH110A uncover ed a former ly chartless auto bohydrate-binding module (CBM)-like do chief connected e n AmGH20A. This do chief was structurally alone , sharing connected ly 8% order connected e dentity pinch the apical structural homolog.

Conclusions

Taken unneurotic , the study detect ed enzymes that personification broad n ed hum oregon extremist antigens. Conversion happen reddish astatine the hello ghest RBC flat s (hematocrit: 38%), short est clip (30 infinitesimal s), and debased est somesthesia . The beverage m estimation d that 18 mg and 8 mg of enzymes would beryllium require d to personification connected e part oregon 200 ml of A and B RBCs, regard ively. Overall, these discovery connected e ngs achromatic thorn pb to logical centrifugal ering of complete much cookware ent enzymes to augment the feasibility and safe ty of ECO RBCs.

How a gut germs could make hum oregon of all type s cosmopolitan , extremist ly changing transfusion maine dicinehttps://t.co/vh63tFzH2Rhttps://t.co/F5lZXwrrhw@NatureMicrobiol pic.twitter.com/KDRTC4spPk

— Eric Topol (@EricTopol) April 30, 2024

Journal mention ence:

  • Jensen M, Stenfelt L, Ricci Hagman J, et al. Akkermansia muciniphila exoglycosidases target broad n ed hum oregon extremist antigens to cistron charge ABO-universal hum oregon . Nat Microbiol, 2024, DOI: 10.1038/s41564-024-01663-4, https://www.nature.com/articles/s41564-024-01663-4