With the hope of designing more effective treatments for tuberculosis (TB), scientists from the U.S. Department of Energy's Brookhaven National Laboratory and collaborating institutions have published the first detailed reports on the biochemistry and structure of a protein-cleaving complex that is essential to the TB bacterium's survival.
The research is published in two papers in the March 2006 issue of Molecular Microbiology, which features a rendition of the "proteasome" structure on its cover.
"Understanding the structure and biochemistry of this proteasome, and how it is different from those found in human cells, could greatly improve prospects for developing specific proteasome-based anti-tuberculosis treatments," said biophysicist Huilin Li, who led Brookhaven's role in the research.
Mycobacterium tuberculosis, the bacterium that causes TB, infects one person in three worldwide. In most infected people, who remain symptom-free, the bacterium is kept in check within immune system cells known as macrophages by compounds such as nitric oxide that kill or disable most bacteria. The current hypothesis is that the compounds work by damaging or destroying proteins, and the accumulated damaged proteins kill the cells if not removed.
The current studies reveal that TB bacteria have a sophisticated way to remove the damaged proteins - a protein-cleaving complex known as a proteasome - with wide specificity for degrading protein parts. This protein cleanup mechanism allows Mycobacterium tuberculosis to remain in macrophages, and possibly go on to cause active TB infections. With details revealed, it could also serve as a target for new anti-TB drugs.
"If we could find a way to specifically inhibit the activity of this Mycobacterium tuberculosis proteasome, then we might have a new, effective treatment for TB," said Li. "Such a treatment might even eradicate TB microbes from infected individuals who show no signs of infection."