Tuberculosis (TB) is not just a disease of the past -- it still kills an estimated three million people every year, and its prevalence is increasing at an alarming rate around the world. TB is caused by the bacterium Mycobacterium tuberculosis, which takes up residence in the lungs of an infected person and wreaks havoc. Now, US researchers report in Nature Structural Biology1that they have worked out the detailed structure of M. tuberculosis 'antigen 85c', a protein that could help combat this disease.

Antigen 85c catalyses an important step in the synthesis of the cell wall -- the resilient coating that surrounds M. tuberculosis, protecting it from environmental assaults (including certain antibiotics). In addition, the immune systems of TB-infected individuals recognize antigen 85c and produce antibodies directed against it.

Tuberculosis has long been a threat to humans. References to TB-like symptoms can be found in the writings of Hippocrates. TB also claimed the lives of many famous individuals, including the Brontës, John Keats and Henry David Thoreau.

In the 1800s, common treatments for TB included induction of lung collapse -- which helped because the bacteria require a high oxygen environment to survive -- and isolation of patients in sanatoria, institutions located away from cities where the air was fresh. Robert Koch discovered the bacteria that cause TB in 1882, and the era of modern medical treatment began in 1944, when the antibiotic 'streptomycin' was first given to an infected person.

Although a vaccine called 'bacille Calmette-Guérin (BCG)' is widely used in developing countries to immunize infants against TB, it is only partially effective. Nevertheless, infection rates declined until the mid 1980s, thanks to the use of anti-TB antibiotics. However, a number of factors, including the HIV/AIDS epidemic and patients' poor compliance with antibiotic treatment regimens, have recently contributed to a worldwide resurgence of this disease. Drug resistant M. tuberculosis strains have begun to emerge. Thus, there is a clear need for new drugs and vaccines to prevent the spread of TB.

James Sacchettini, of Texas A&M University in the USA, and his co-workers determined the structure of antigen 85c using X-ray crystallography, a method that reveals details at the level of individual atoms, by extrapolating back, mathematically, from the way that they scatter X-ray radiation. The structure helps to explain how antigen 85c performs its catalytic role and also confirms that the immune-sensitive regions are highly exposed on the surface of the protein.

Antigen 85c is potentially a good target for the development of novel drugs and vaccines. For instance, the bacteria that cause TB could be made more vulnerable if cell-wall construction were stalled by turning off this protein's activity with drugs that bind to it. Plus, if the immune-sensitive parts of the protein could be produced in isolation and safely injected into people, they could be used to elicit antibody production. In other words, researchers might have the makings of an effective vaccine.

The new structural information should allow scientists to make better guesses about which drugs might interact most effectively with antigen 85c and should also help in pinpointing the surface regions to use in vaccine development.