Turning universal O into rare Bombay type blood
Itxaso Anso, Andreas Naegeli, Javier O. Cifuente, Ane Orrantia, Erica Andersson, Olatz Zenarruzabeitia, Alicia Moraleda-Montoya, Mikel García-Alija, Francisco Corzana, Rafael Del Orbe, Francisco Borrego, Beatriz Trastoy, Jonathan Sjögren, Marcelo E. Guerin
Abstract
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 h Bombay phenotype, can only be transfused with group O h 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.