Scientists crack genome sequence of Johne's disease pathogen

St. Paul-Unlocking the gene sequencing of Johne's disease will undoubtedly lead to improved diagnostics and vaccines to fight the disease, a Johne's expert says.

In late November, University of Minnesota researchers with collaboratorsat the United States Department of Agriculture's (USDA) National AnimalDisease Center in Ames, Iowa announced they completed sequencing the genomeof Mycobacterium paratuberculosis, a chronic wasting disease of dairy cattleestimated at costing the industry $200 million in losses. Vivek Kapur, BVSc,Ph.D., principal investigator, is director of the university's AdvancedGenetic Analysis Center and co-director of the Biomedical Genomics Centerat the University of Minnesota (UM). John Bannantine, Ph.D., was a co-investigatorat USDA's National Animal Disease Center.

The Johne's breakthrough is a notable scientific achievement, says Dr.Don Hansen, who serves on the National Johne's Working Group of the UnitedStates Animal Health Association. The Johne's working group was createdin 1995 to develop and expedite implementation of a strategic plan to controlM. paratuberculosis (Johne's disease) in U.S. cattle herds.

Hansen who speaks to veterinarians and producers nationally about Johne'sdisease, says of the gene sequencing work, "Maybe we will now discovermore about the mechanism of its transmission, mechanism for its spread ora mechanism to detect it at an early stage. All of those are on the tablenow for these guys that wheel and deal in the genome to unravel. I am incrediblyhopeful."

Frustrating problem

Mycobacterium paratuberculosis is considered one of the most importantthreats to the health of dairy cattle worldwide, and may represent a potentialrisk to safety of the milk supply.

"This is a horrible, hard to diagnose disease, largely because welacked an understanding of the basic genetic make-up of the organism andthe tools to differentiate the bacterium from other closely related species,"says Kapur, principal investigator of the research project.

"The genome sequence sheds new light on the genes and biochemicalpathways in the bacterium, and the research offers a starting point fordefining the mechanisms by which the organism causes disease and helpingdevise new strategies to detect infected animals and ultimately help controlthe spread of the organism," he says.

M. paratuberculosis is a slow-growing bacterium that causes a chronicgastrointestinal infection in dairy cattle and other small ruminant species(such as sheep, goat and deer) and has both serious health and economicconsequences to dairy farming worldwide.

During the sequencing project, scientists discovered several genes thatmay help differentiate M. paratuberculosis from other closely related bacterialspecies. "The genes we've identified will serve as targets for thedevelopment of new generations of diagnostic tests that are critically neededfor the detection and ultimate eradication of the disease," says Bannantine,of USDA's National Animal Disease Center.

The analysis of the M. paratuberculosis genome found that its sequencecontains nearly 5 million base pairs that are represented on a large circularchromosome with more than 4,500 predicted genes, USDA reports. The researchersalso found that the chromosome has a large number of sequences repeatedthroughout the genome. The identification of all of the genes and key metabolicpathways in this organism may serve to explain some of the unique aspectsof the biology of the pathogen, including its slow growth in laboratoryculture (which can take up to six months).

"The slow-growing nature of this bacterium has been an impedimentto the diagnosis of infected animals and has also served as a major obstaclefor laboratory based research on the pathogen," says Kapur.

The sequencing project represents part of a "microbial pathogenomics"research program at the University of Minnesota. Its mission is to sequencethe genomes of a wide range of human and animal pathogens and then use theinformation to better understand these diseases.

The genome project is hoped to spur development of the new or improvedantimicrobial agents and vaccines to protect cattle against infection withthe bacterium.

Congress believes controlling the disease is so important, the U.S. HouseAgriculture Appropriations Subcommittee recently approved $20.3 millionfor a National Johne's Disease Management and Testing Program for the currentfiscal year. The appropriation is pending approval in the U.S. Senate.

Sponsored programs

Hansen says that in today's dairy industry, there are a number of diseasesthat producers should be vigilant, especially diseases with a fecal/oraltransmission route like scours, salmonella and Johne's disease.

The latest genetics discovery comes in the wake of an organized pushto educate producers about Johne's disease.

Why? Hansen explains, "I personally think that the potential linkbetween Mycobacterium paratuberculosis and Crohn's disease in humans isenough to give impetus to controlling the disease in cattle herds. We aresaying 'what if' this link exists. If we can do something proactive, weare going to be in a much better position if it turns out that way,"Hansen says.

Hansen adds, "I have been associated with producers trying to fighttheir way through Johne's disease ever since I graduated in 1972."

To fight Johne's disease, USAHA and USDA collaborated on a voluntaryJohne's disease status program. To enter the program, producers make a publicdeclaration of their intent to fight the disease. The program has been segmentedinto four levels. Admittance into each level progressively improves therisk of a herd being free of Johne's disease. The program mandates producerswork with veterinarians to identify Johne's cows, draft a management andrisk assessment plan.

Hansen explains, "With each level, there is an increased probabilitythat the herd is free of infection." Each level has testing requirementsevery 12 to 14 months, because M. paratuberculosis is such a slow-growingbacteria. For veterinarians, it can be a frustrating disease to diagnose,simply because in the early stages it may be shedding at such low levelsdiagnostic tests can miss it. And the bacteria can be circulating in a herdfor up to two years before any animals show clinical signs.

The basics of prevention are straightforward, USAHA adds.

* Prevent infections by closing the herd from animal additionsor securing additions or replacements from Johne's-free or Johne's test-negativeherds.

* In herds where infection is already present, additional stepsinclude identification manure management, colostrum or milk management ofinfected animals and removal or separation from the herd and by cullingoffspring of known infected mothers.

Go to www.usaha.org for more information on Johne's prevention strategies.