Why TB is so hard to Shake Off

Researchers at the Memorial Sloan-Kettering Cancer Center have identified one way in which the bacteria that causes TB can evade our defences.

Tuberculosis is a killer.  Each year, 8 million people become infected with TB, and 2 million die from the disease.  It's the world's leading infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS.  The World Health Organisation estimates that nearly 2 billion people have been exposed to Mycobacterium tuberculosis, the bacteria that causes TB.

One of the reasons TB is such a problem is that it can evade the body's immune system by modifying its own growth rate - slowing the metabolic processes down so much that it becomes resistant to the DNA damaging chemicals produced by the macrophage, the immune system cell in which it lives.

Writing in the journal Cell, Michael Glickman and colleagues have identified a protein, called CarD, that helps the bacterium lie low.  CarD binds to RNA polymerase, the protein that transcribes DNA into RNA, and slows the production of ribosomal RNA (rRNA).  rRNA is used in protein manufacture, and accounts for 90% of all transcription.  Removing CarD is fatal to the bacterium, as it leaves it more sensitive to attack.

This could lead to a new avenue of attack, essential if we are to tackle drug resistant strains of TB, and as CarD is found in many species of bacteria, including the bacterium that causes Anthrax, may have wider implications.

"The TB health crisis is exacerbated by the alarming emergence of multidrug- and extensively drug-resistant strains," Glickman said. "The development of new chemotherapeutic strategies is imperative, which requires insight into the pathways involved in M. tuberculosis infection, persistence, and drug resistance. CarD is one such pathway that we plan on targeting for therapeutic development. "