In July 2018, Red Cross issued an urgent call for blood donors because their stock was depleted. They provide blood to hospitals around the country in the USA, so they must keep a 5-day supply of blood in case of medical emergencies. While all blood types are equally important, there is an especially high demand for type-O blood. Type O-positive is the most transfused blood type because it can be given to any patients with Rh-positive blood type. Meanwhile, Type-O negative is a universal donor and can be given to patients of any blood type.
Why is this important?
Eight different blood types can be categorized into four groups based on their antigens: A, B, AB, and O. Antigens are molecules that act as a defense mechanism of the body. It can detect the presence of foreign objects and help produce antibodies to fight the foreign object. An individual with type-A blood has type-A antigen and will produce antibodies against the type-B antigen. The antibodies produced can cause life-threating immune reactions in the host body. However, type-O blood has no antigen. Therefore it can safely be transfused without any risk of reactions.
Dr. Stephen Withers and his team of researchers at the University of British Columbia were able to find an enzyme that can safely remove the antigens from different blood types. Once the antigens are removed, they are essentially identical to type-O blood and safe for a wider range of people.
How was it done?
They used two high-throughput methodologies:
- They selected specific glycoside hydrolase families of interest and created a phylogenetically distinct sub-families of their genes. From each sub-family, they selected a representative gene and expressed it in E.coli.
- Total DNA from an environment of interest (such as the human gut, beaver feces, and so on) was extracted using metagenomics and expressed in E.coli.
Using metagenomics allows for DNA sequencing of millions of microorganisms at the same time. Their research eventually led them to focus on the mucosal lining of the human gut, which contains sugars that are similar in structure to blood antigens. They were then able to “use E. coli to select for DNA containing genes that code for enzymes that can cleave sugar residues.” The researchers then multiplied the enzymes and found that it was capable of removes the Gal or GalNAc residues that determine the antigens of type-A and type-B blood, which essentially makes the blood type-O.
Relevant Video
Dr. Stephen G. Withers presented his findings at the 256 ACS National Meeting & Exposition in August 2018 in Boston, MA. His talk was titled “Discovery of CAZYmes for cell surface glycan removal through metagenomics: Towards universal blood“.