Type A blood converted to universal donor blood with help from bacterial enzymes

117.4 million blood donations collected globally for emergency surgeries, scheduled operations, and routine transfusions. But recipients can’t take just any blood: For a transfusion to be successful, the patient and donor blood types must be compatible. Now, researchers analyzing bacteria in the human gut have discovered that microbes there produce two enzymes that can convert the common type A into a more universally accepted type. If the process pans out, blood specialists suggest it could revolutionize blood donation and transfusion.
“This is a first, and if these data can be replicated, it is certainly a major advance,” says Harvey Klein,  a blood transfusion expert at the National Institutes of Health’s Clinical Center in Bethesda, Maryland, who was not involved with the work.

People typically have one of four blood types—A, B, AB, or O—defined by unusual sugar molecules on the surfaces of their red blood cells. If a person with type A receives type B blood, or vice versa, these molecules, called blood antigens, can cause the immune system to mount a deadly attack on the red blood cells. But type O cells lack these antigens, making it possible to transfuse that blood type into anyone. That makes this “universal” blood especially important in emergency rooms, where nurses and doctors may not have time to determine an accident victim’s blood type.

“Around the United States and the rest of the world, there is a constant shortage,” says Mohandas Narla, a red blood cell physiologist at the New York Blood Center in New York City.
To up the supply of universal blood, scientists have tried transforming the second most common blood, type A, by removing its “A-defining” antigens. But they’ve met with limited success, as the known enzymes that can strip the red blood cell of the offending sugars aren’t efficient enough to do the job economically.
After 4 years of trying to improve on those enzymes, a team led by Stephen Withers, a chemical biologist at the University of British Columbia (UBC) in Vancouver, Canada, decided to look for a better one among human gut bacteria. Some of these microbes latch onto the gut wall, where they “eat” the sugar-protein combos called mucins that line it. Mucins’ sugars are similar to the type-defining ones on red blood cells.
So UBC postdoc Peter Rahfeld collected a human stool sample and isolated its DNA, which in theory would include genes that encode the bacterial enzymes that digest mucins. Chopping this DNA up and loading different pieces into copies of the commonly used lab bacterium Escherichia coli, the researchers monitored whether any of the microbes subsequently produced proteins with the ability to remove A-defining sugars.


At first, they didn’t see anything promising. But when they tested two of the resulting enzymes at once—adding them to substances that would glow if the sugars were removed—the sugars came right off. The enzymes also worked their magic in human blood. The enzymes originally come from a gut bacterium called Flavonifractor plautii, Rahfeld, Withers, and their colleagues report today in Nature Microbiology. Tiny amounts added to a unit of type A blood could get rid of the offending sugars, they found. “The findings are very promising in terms of their practical utility,” Narla says. In the United States, type A blood makes up just under one-third of the supply, meaning the availability of “universal” donor blood could almost double.
But Narla says more work is needed to ensure that all the offending A antigens have been removed, a problem in previous efforts. And Withers says researchers need to make sure the microbial enzymes have not inadvertently altered anything else on the red blood cell that could produce problems. For now, the researchers are focusing on only converting type A, as it’s more common than type B blood. Having the ability to transform type A to type O, Withers says, “would broaden our supply of blood and ease these shortages.”