Animal & Veterinary
OR on the Cutting-Edge of Research
By Dr. Carmela Stamper, Contributing Writer/Editor, Communications, with contributions from Dr. Michael Myers, Research Pharmacologist, Dr. Jamie Boehmer, Biologist, and Dr. Haile Yancy, Biologist, Division of Animal Research, and Dr. Heather Harbottle, Microbiologist, Division of Animal Food and Microbiology
CVM’s Office of Research (OR) is working on several exciting and cutting-edge scientific projects with biomarkers. Biomarkers, or biological markers, are substances found in the body that scientists can measure to study a biological process or condition, such as aging, a specific disease, or exposure to a toxin. OR’s projects are designed to identify biomarkers associated with:
- Inflammation in dairy cows and dairy goats that have coliform mastitis. In coliform mastitis, the mammary gland becomes inflamed due to infection with the bacteria Escherichia coli (E. coli) and the bacteria’s release of toxins called lipopolysaccharides (LPS);
- Inflammation in swine (pigs);
- Salmonella bacteria; and
- A genetic defect in herding dog breeds.
The dairy cow and dairy goat projects, conducted by Dr. Jamie Boehmer, and the swine project, run by Dr. Michael Myers, will provide useful information about the inflammatory process in ruminants (animals like cows, goats, and sheep) and pigs. This information can be used to better design effectiveness studies for anti-inflammatory drugs in food-producing animals. If a specific “inflammation biomarker” is identified, a drug company may be able to measure this biomarker to show that an anti-inflammatory drug is effective. In a dairy cow with an infected mammary gland or a pig with a sore foot, the levels of these “inflammation biomarkers” should change. After treating the animal with an anti-inflammatory drug, the levels should return to normal if the drug is effective at reducing inflammation. If the biomarker levels do not return to normal, the drug may not be effective.
Currently, no drugs are approved to treat inflammation in pigs, and researchers also do not have a good way to test how well an anti-inflammatory drug works in pigs. Finding biomarkers associated with inflammation in swine will help researchers develop needed anti-inflammatory drugs.
The Salmonella project, run by Dr. Heather Harbottle and Mr. Scott Jackson, from FDA’s Center for Food Safety and Applied Nutrition (CFSAN), will give researchers valuable human food safety and public health information. One project goal is to find Salmonella biomarkers that can be used during an outbreak to trace the source of the Salmonella bacteria, if the source is animal-related. Scientists can use this information to pinpoint where food likely became contaminated in the food processing chain. Another project goal is to see if Salmonella biomarkers can be used to identify animal-related sources of drug resistance. If the source of resistance to a certain drug is known, the risk of more resistance developing can be minimized.
The herding dog breeds project, conducted by Drs. Michael Myers and Haile Yancy, will provide important animal health information for veterinarians and breeders of herding dogs. The OR scientists are studying a genetic defect seen in Collies and other herding dogs that causes changes to an important protein. The protein, P-glycoprotein (P-gp), is found in the cell membrane (the thin sheet that covers the cell). The normal protein protects the cell by pumping harmful chemicals from inside the cell to the outside. In Collies and other herding dogs with the genetic defect, the changes in the protein cause the cell membrane’s pump to not function, so the harmful chemicals remain inside the cell. This makes the dogs more sensitive to drugs that are transported out of the cell by P-gp, including an important class of drugs called avermectins.
Ivermectin is an avermectin used in dogs to treat intestinal worm infections and prevent heartworm disease. In normal dogs with the normal protein, ivermectin is transported out of the cell by P-gp and does not build up inside the cell. These dogs are not prone to ivermectin toxicity.
A genetic test is available to see if a Collie or other herding dog is homozygous or heterozygous for the defective P-gp. If the dog is homozygous, it has two identical copies of the gene that code for the defective protein. When given drugs like ivermectin, homozygous dogs are prone to drug toxicity.
If the dog is heterozygous, it has two different copies of the gene: one copy codes for the defective protein and one copy codes for the normal protein. Because heterozygous dogs have one defective gene, they are considered sensitive to drugs that are transported by P-gp. When given ivermectin, they show signs of toxicity. However, Drs. Myers and Yancy have uncovered an interesting finding that some heterozygous dogs are not sensitive to ivermectin. Also, the heterozygous dogs that are sensitive to ivermectin are not always sensitive to other drugs that are transported by P-gp.
Drs. Myers and Yancy are now looking for a genetic difference between the heterozygous dogs that are sensitive to ivermectin and the heterozygous dogs that are not sensitive. If a genetic difference is found, scientists can then create a new test to detect this difference. Such a test will help veterinarians more safely treat their herding dog patients and help breeders of herding dogs improve their breeding stock.
From dairy cows with mastitis to disease-causing Salmonella bacteria, OR scientists are hard at work discovering new tools to protect human and animal health.