Protein On TB Bacteria
May Hold Key To
New Treatment

NEW YORK (Reuters Health) - Researchers studying the bacterium that causes tuberculosis (TB) have found that a protein on the pathogen's surface may hold the key to a new vaccine or treatment for the disease, which kills about 3 million people worldwide each year.
In the February issue of Nature Structural Biology, researchers led by Dr. James Sacchettini, of Texas A University in College Station, report that the structure of a protein complex called antigen 85c reveals potential targets for TB vaccines and drugs. Antigen 85c plays a major role in constructing the TB bacterium's cell wall, a particularly hardy wall that helps the bacterium infect body cells and often protects it from current TB drugs.
Using x-ray crystallography, an imaging technique that reveals structural details of individual atoms, Sacchettini's team was able to study the structure of antigen 85c and observe how the protein helps the TB bacterium infect immune-system cells. Experts believe that understanding antigen 85c's structure could lead to new TB treatments -- if, for example, drugs could turn off the protein's activity in maintaining the bacterium's cell wall, this would stall cell-wall construction and leave the pathogen vulnerable.
In an editorial accompanying the report, Dr. Peter J. Tonge of the State University of New York at Stony Brook, calls antigen 85c ``an exciting new target in the fight against tuberculosis.'' ``Clearly,'' he writes, ``cell wall assembly is a profitable choice for the design of novel antitubercular compounds.''
Scientists have also known that the immune system recognizes antigen 85c upon infection with TB, making the protein a good target for vaccines. The only TB vaccine now available, and widely used in developing countries, is often ineffective. Sacchettini and his colleagues found that the areas of antigen 85c that are vulnerable to the immune system are highly exposed on the protein's surface; this suggests that if these immune-sensitive areas can be produced in the lab and safely administered, they may make an effective TB vaccine.
While no longer the killer it was before the 20th century, TB remains a global problem. About one third of the world's population is infected with TB, including, according to the National Institutes of Health (NIH), between 10 and 15 million Americans. However, since the immune system can usually fight off the infection, only an estimated 10% of those infected develop TB. Coughing, breathing difficulty, weight loss, and fever are often symptoms of TB, an air-borne infection that usually begins in the lungs.
TB had been declining in the United States until the mid-1980s, when various factors spurred an increase in TB cases. Such factors included poor compliance with antibiotic treatment and the susceptibility of people with AIDS to developing the disease. In addition, according to the NIH, 43 states had reported cases of multidrug-resistant TB by 1997, compared with 13 states in 1991. SOURCE: Nature Structural Biology 2000;7:94-95, 141-143.


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