Turning universal O into rare Bombay type blood.

Anso, Itxaso; Naegeli, Andreas; Cifuente, Javier O; Orrantia, Ane; Andersson, Erica; Zenarruzabeitia, Olatz; Moraleda-Montoya, Alicia; García-Alija, Mikel et al. · Nat Commun · 2023

basic_science · Level V

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Abstract

Red blood cell antigens play critical roles in blood transfusion since donor incompatibilities can be lethal. Recipients with the rare total deficiency in H antigen, the O<sub>h</sub> Bombay phenotype, can only be transfused with group O<sub>h</sub> blood to avoid serious transfusion reactions. We discover FucOB from the mucin-degrading bacteria Akkermansia muciniphila as an α-1,2-fucosidase able to hydrolyze Type I, Type II, Type III and Type V H antigens to obtain the afucosylated Bombay phenotype in vitro. X-ray crystal structures of FucOB show a three-domain architecture, including a GH95 glycoside hydrolase. The structural data together with site-directed mutagenesis, enzymatic activity and computational methods provide molecular insights into substrate specificity and catalysis. Furthermore, using agglutination tests and flow cytometry-based techniques, we demonstrate the ability of FucOB to convert universal O type into rare Bombay type blood, providing exciting possibilities to facilitate transfusion in recipients/patients with Bombay phenotype.

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