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Genome sequence of Johne`s disease pathogen cracked
Researchers from the University of Minnesota with collaborators at the United States Department of Agriculture`s (USDA) National Animal Disease Center in Ames, Iowa announced they completed sequencing the genome of Mycobacterium paratuberculosis. Johne´s disease, a chronic wasting disease of dairy cattle estimated at costing the industry $200 million in losses. Knowing the genome will improve both diagnostic and vaccine possibilities.

Vivek Kapur, BVSc, Ph.D., principal investigator, is director of the university`s Advanced Genetic Analysis Center and co-director of the Biomedical Genomics Center at the University of Minnesota (UM). John Bannantine, Ph.D., was a co-investigator at USDA`s National Animal Disease Center. 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.

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

Hansen who speaks to veterinarians and producers nationally about Johne`s disease, says of the gene sequencing work, `Maybe we will now discover more about the mechanism of its transmission, mechanism for its spread or a mechanism to detect it at an early stage. All of those are on the table now for these guys that wheel and deal in the genome to unravel. I am incredibly hopeful.`

Frustrating problem

Mycobacterium paratuberculosis is considered one of the most important threats to the health of dairy cattle worldwide, and may represent a potential risk to safety of the milk supply.

`This is a horrible, hard to diagnose disease, largely because we lacked an understanding of the basic genetic make-up of the organism and the 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 biochemical pathways in the bacterium, and the research offers a starting point for defining the mechanisms by which the organism causes disease and helping devise new strategies to detect infected animals and ultimately help control the spread of the organism,` he says.

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

During the sequencing project, scientists discovered several genes that may help differentiate M. paratuberculosis from other closely related bacterial species. `The genes we`ve identified will serve as targets for the development of new generations of diagnostic tests that are critically needed for 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 sequence contains nearly 5 million base pairs that are represented on a large circular chromosome with more than 4,500 predicted genes, USDA reports. The researchers also found that the chromosome has a large number of sequences repeated throughout the genome. The identification of all of the genes and key metabolic pathways in this organism may serve to explain some of the unique aspects of the biology of the pathogen, including its slow growth in laboratory culture (which can take up to six months).

`The slow-growing nature of this bacterium has been an impediment to the diagnosis of infected animals and has also served as a major obstacle for 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 sequence the genomes of a wide range of human and animal pathogens and then use the information to better understand these diseases.

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

Congress believes controlling the disease is so important, the U.S. House Agriculture Appropriations Subcommittee recently approved $20.3 million for a National Johne`s Disease Management and Testing Program for the current fiscal 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 diseases that producers should be vigilant, especially diseases with a fecal/oral transmission route like scours, salmonella and Johne`s disease.

The latest genetics discovery comes in the wake of an organized push to educate producers about Johne`s disease.

Why? Hansen explains, `I personally think that the potential link between Mycobacterium paratuberculosis and Crohn`s disease in humans is enough to give impetus to controlling the disease in cattle herds. We are saying `what if` this link exists. If we can do something proactive, we are 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 fight their way through Johne`s disease ever since I graduated in 1972.`

To fight Johne`s disease, USAHA and USDA collaborated on a voluntary Johne`s disease status program. To enter the program, producers make a public declaration of their intent to fight the disease. The program has been segmented into four levels. Admittance into each level progressively improves the risk of a herd being free of Johne`s disease. The program mandates producers work with veterinarians to identify Johne`s cows, draft a management and risk assessment plan.

Hansen explains, `With each level, there is an increased probability that the herd is free of infection.` Each level has testing requirements every 12 to 14 months, because M. paratuberculosis is such a slow-growing bacteria. For veterinarians, it can be a frustrating disease to diagnose, simply because in the early stages it may be shedding at such low levels diagnostic tests can miss it. And the bacteria can be circulating in a herd for 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 additions or securing additions or replacements from Johne`s-free or Johne`s test-negative herds.

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

Source: Daniel R. Verdon (2003): Scientists crack genome sequence of Johne`s disease pathogen. In: DVM Newsmagazine January 1, 2003.

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