May 23, 2003
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."
"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).
TB & Outbreaks Week