Research Focuses On Mycobacterial Diseases

US - Tuberculosis kills humans at the rate of one every 15-20 seconds, while bovine tuberculosis and Johne's disease can cause economic losses in the range of billions to the beef and dairy cattle industries.
calendar icon 22 February 2010
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Raul Barletta and Ofelia Barletta-Chacon are conducting research that aims to find integrated approaches to treating mycobacterial diseases in both humans and animals.

What ties these diseases together is that all are caused by mycobacteria, bacteria with unusually thick, waxy cell walls that make them especially hardy and difficult to fight. Mycobacteria are naturally resistant to many antibiotics that work by destroying cell walls.

University of Nebraska-Lincoln scientists hope to develop approaches in vaccination, diagnosis and treatment that could be adapted to all mycobacterial diseases, whether they strike human beings or animals.

"We want to find an integrated approach to mycobacterial diseases so we can apply the knowledge of one to another," said Ofelia Barletta-Chacon, a physician and microbiologist with more than 20 years of experience with tuberculosis, who's conducting research with her husband, Raul Barletta, a microbiologist with more than 25 years of experience with mycobacteria.

Tuberculosis, caused by Mycobacterium tuberculosis, kills millions every year, and about 2 billion people – one-third of the world population – are infected with the TB-causing bacilli. Although tuberculosis is treatable, the incorrect as well as erratic use of therapy often leads to the development of resistance to available regimens, Mr Barletta said. In addition, the AIDS epidemic has accentuated the problem of drug-resistance tuberculosis, thanks to higher microbial burdens, treatment non-compliance, and a limited drug repertoire because of side effects from the interactions of anti-tuberculosis and AIDS medications.

Especially problematic are the TB strains known as MDR (moderately drug resistant) and XDR (extensively drug-resistant). "Right now there is no way to treat it, and it's very lethal," Ms Barletta-Chacon said.

It's estimated that 490,000 new cases of MDR-TB emerged in 2006 with 110,000 deaths, and it's estimated 40,000 new cases of XDR-TB emerge every year. "Those reported numbers, however, are believed to capture only a small percentage of the actual cases," Mr Barletta said.

"Current antibiotics for mycobacterial diseases tend to target a single enzyme for inhibition, so a single mutation in the enzyme can render them ineffective," he said. Institute of Agriculture and Natural Resources researchers' goal is to develop antibiotics that target multiple enzymes so they're more effective.

They're also focusing on related livestock diseases.

"Bovine tuberculosis can be devastating economically, as its discovery in an animal requires its destruction and, potentially, culling of other animals," Mr Barletta said.

The scientists hope their research will lead to vaccines to prevent bovine tuberculosis, as well as tools to provide more accurate, faster diagnoses in the field. "Inaccurate results are not unusual with current tests. A false positive bovine tuberculosis test, even if later overturned by more extensive testing, can do great economic damage," Mr Barletta said.

Mycobacterium paratuberculosis causes Johne's disease, a contagious, chronic and sometimes fatal infection that strikes ruminants. There is some evidence the same pathogen is connected with Crohn's disease in humans, an inflammatory disease of the intestines.

"The similarity between the agents causing these diseases can be exploited to apply knowledge from one to another. Knowledge derived from the human pathogen can be applied to the animal pathogen and vice-versa. For example, when the first finished mycobacterial genome was published, it was from a human pathogen. We successfully applied it to look for genes important for disease in animals," he said.

Funding for the research comes from the US Department of Agriculture, World Health Organization, National Research Initiative, National Institutes of Health and the United States-Israel Binational Agricultural Research and Development Fund. The research also includes scientists from the departments of chemistry; chemical and biomolecular engineering; biological sciences; and food science and technology.

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