We killed it

THERE are some pathogens that disguise themselves and prevent detection by the host's immune system. There are others that save themselves by mimicking the defence molecules produced by the host's body. Then there is the tuberculosis bacterium.

Regarded as the world's most successful infectious agent, the bacterium Mycobacterium tuberculosis kills 1.3 million people every year. 30 per cent of the world's population is infected with the MICROBIOLOGY: drug discovery We killed it TB bacterium plays dead, immune cells are fooled PHYSIOLOGY: energy conservation The way you swing A weight-loss tip: do not swing the arms while walking bacterium, but the infected do not know it; there are no symptoms. It is the same when seen from a micro-scale: the macrophages sent out by the human body to kill it end up housing the pathogen without realizing it.

Macrophages are white blood cells that engulf and digest pathogens. They swallow the tuberculosis bacterium with the same intention but the bacterium undoes their efforts. Once inside the macrophage, it enters a near-dormant state by controlling its growth rate. For the macrophage it is as good as dead. In this manner, the pathogen makes a successful entry into the host's body. What the bacterium does is control the rate of formation of RNA from DNA. This, in turn, controls the formation of many proteins needed for growth and development.

The team identified the key protein, called CarD, that directs the bacterium to act this way. This protein binds to a an enzyme called the RNA polymerase and inhibits the formation of RNA. Hence CarD is the ticket to the bacte - rium's survival in the host's body.

Glickman and his team found that stress signalled the gene encoding for the CarD protein to express the protein in larger amounts. When scientists cultured modified strains without the gene, large numbers of bacteria died. In lab cultures, the protein's absence made them vulnerable to DNA damage, oxidative stress and lack of nutrients. In infected mice, absence of the protein led the macrophages to kill their targets.

Targeting the CarD protein with molecules that destroy its capabilities might be just what TB drug manufacturers should keep in mind.

The CarD protein is widely distributed in the bacterial world. It is found in Bacillus anthracis, the bacterium that causes anthrax. "Hence this finding may have broader applications in targeting other important pathogens," said Glickman. The study is in the July 10 issue of Cell.

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