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Scientists Find Genetic Key to TB Bacteria Survival in Lung Cells

May 23, 2003


This article is part of The Body PRO's archive. Because it contains information that may no longer be accurate, this article should only be considered a historical document.

New research led by University of North Carolina -- Chapel Hill scientists shows for the first time how Mycobacterium tuberculosis uses a system for releasing proteins to help it survive the lungs' immune defenses to spread and cause disease. The study adds crucial new knowledge to the molecular factors that underlie the virulence of M. tuberculosis and may aid development of new, targeted treatments for the disease. "I think this study moves us along in our understanding of TB pathogenesis," said lead author Dr. Miriam Braunstein, assistant professor of microbiology and immunology at UNC's School of Medicine.

Braunstein and colleagues said numerous disease-causing bacteria "possess specialized protein secretion systems that are dedicated to the export of virulence factors." The TB bacillus possesses in its genome the genes secA1 and secA2, researchers said. In a previous report, Braunstein and others had shown that the protein SecA1 is essential for the bacillus, whereas SecA2 is not. Both of these proteins are similar to SecA, a protein that functions in the secretion process of all other bacteria. However, the presence of multiple SecA proteins in a single bacterium is highly unusual and only shared with a few other pathogenic bacteria.

"In this study, we wanted to see if the two SecAs do the same thing or have different functions," Braunstein said. "We had a hunch that SecA2 was involved in the bacteria's virulence, that it might be dedicated to secreting a specific subset of proteins involved in virulence."

Testing the hypothesis, Braunstein and colleagues engineered a mutant strain of tuberculosis that did not have secA2, so was unable to produce protein SecA2. Mice infected with the mutant strain survived longer than mice infected with TB containing secA2, said Braunstein. Research showed the same thing in terms of bacterial growth in the lung, liver and spleen. "When TB is missing SecA2, it is less virulent. There is less bacterial growth, especially in the lung."

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The next step was to identify the virulence factor secreted by the protein. Two of the proteins dependent on SecA2 were antioxidant molecules: superoxide dismutase-A and catalase-peroxidase. When M. tuberculosis is inhaled and enter the aveoli, the bacterium becomes attacked and engulfed by macrophages. But where other bacteria succumb to the attack, TB survives, having evolved over time to overcome the "oxidative burst" leveled at it.

"These SecA2-depedent secretions, superoxide dismutase-A and catalase-peroxidase, are enzymes that actually scavenge the oxygen radicals that are shot at the bacteria," said Braunstein. Someday, drugs against TB infection could be developed that block this secretion system, said Braunstein. The full report, "SecA2 Functions in the Secretion of Superoxide Dismutase A and in the Virulence of Mycobacterium tuberculosis," appeared in the April issue of Molecular Microbiology (2003;48(2):453-464).

Back to other CDC news for May 23, 2003

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Adapted from:
TB & Outbreaks Week
05.06.03




This article was provided by CDC National Prevention Information Network. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update.
 

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