Udder Disease: Plant BioFactory Ramps Up Relief for Dairy Cows

Agricultural Research Service (ARS) scientists are testing a plant-produced, therapeutic protein, which thwarts bacteria that cause inflammatory udder disease in dairy cows. They turned a laboratory-produced plant virus into a delivery vehicle that carries a specific gene. The target gene expresses large quantities of a protein called CD14. When the virus reproduces itself inside plant cells, it generates CD14.

The researchers designed the virus to use the plant as a patent-pending "biofactory" that rapidly accumulates usable quantities of the therapeutic CD14 protein. A tagging system—which the researchers built into the technology—allows high levels of the CD14 protein to be harvested from mashed leaves. Potentially, fifty plants could provide enough purified protein to treat a herd of 500 cows.

The CD14 protein is naturally present in cows' milk and blood plasma. Increased amounts of the protein in body fluids may help improve protection against bacterial attack. CD14 binds to and neutralizes a toxin which is present in the outer membrane of the bacterium Escherichia coli that causes mastitis. This binding enhances the cow's immune response, which contributes to a rapid clearance of bacteria before infection gains a foothold.

ARS molecular biologist Lev Nemchinov and plant pathologist Rosemarie Hammond produced the unique plant virus at the agency's Molecular Plant Pathology Laboratory in Beltsville, Md. After a small drop of the virus' transmittable RNA has been rubbed onto plant leaves, the CD14 gene begins to make the protein.

ARS colleagues infused the protein into one of a test cow's four teats, or quarters. All four quarters were then exposed to E. coli. Fewer viable bacteria were recovered from the quarter that received the CD14 treatment than from those that did not receive the plant-derived protein.

Mastitis costs dairy farmers billions annually from incapacitated cows and milk that can't be sold, according to experts.

Coliform mastitis is the most prevalent form of clinical mastitis in the dairy industry and is mainly caused by the Escherichia coli bacterium. Use of antibiotics to control mastitis infections can be expensive and carries with it concerns about the emergence of antibiotic-resistant bacteria. Yet mastitis is expensive too, costing dairy farmers an estimated $2 billion annually from incapacitated cows and milk that can’t be sold.

ARS has applied for patent protection on the plant-derived CD14, and the researchers are now seeking partners to help further develop and test the protein for safety, effectiveness, and proper dosage.

“As a next step, we’d like to work with a commercial partner to produce large volumes of plant-made CD14 and then conduct further tests to determine the most effective dosages in cows to achieve maximal protection from infection,” says Hammond. “We may not need as much as the 100 micrograms per dose that we used in our first tests. Further studies may show that we can achieve the same results with less protein.”

The CD14-based product may eventually be commercially developed for use by dairy farmers as a treatment to prevent cows from becoming infected during their dry period. Dairy cows are milked for 305 days and then enter a 60-day dry period, during which they are most susceptible to coliform infections. The plant-made CD14 could be incorporated into a polymer and infused into the udder during dry-off. The polymer would allow slow release throughout the dry period to help fight infections.