Nature Cell Biology 5, pp 793 - 802

Tuberculosis results in 2 million deaths each year world wide, and about 8 million new cases are reported annually. As such, it is the leading cause of death from a bacterial disease. Now, Gareth Griffiths and colleagues, in a study published in the September issue of Nature Cell Biology, suggest that dietary lipids may help overcome such infections in animal models.

The causative agent of tuberculosis — a bacterium called Mycobacterium tuberculosis — infects white blood cells where it is held in a specialized membraneous sac called phagosomes. Normally, the phagosome would mature into a compartment containing degradative enzymes that would break down phagosomal contents. Although scientists have known for some time that Mycobacterium blocks phagosome maturation, exactly how the bacterium does this is not known.

This new study might not only explain how the bacterium could subvert normal phagosome maturation, but might also suggest new avenues for treating tuberculosis. The authors show that phagosomes containing the bacterium are unable to support the nucleation of actin, a component of the cell's skeletal network that seems to be important for phagosome maturation. Most remarkably, this study shows that certain natural lipids can reverse the inhibition of actin nucleation by the infected phagosome, stimulate phagosomal maturation in infected cells, and lower the survival rate of the pathogen in infected cells.

Whether dietary lipids might one day become a feasible way to treat tuberculosis remains to be determined. However, based on their findings, the authors recommend testing the effectiveness of these lipids to overcome infections in animal models.

Nature Cell Biology 5, pp 834 - 839

RNA interference - a technique that has recently emerged as the tool of choice in the laboratory and one that is also being explored for therapeutic purposes - may not be as specific as previously thought, reports a new study published in the September issue of Nature Cell Biology. The specificity of this approach is crucial to its success both in the laboratory and in the hospital.

The technique involves using short RNA sequences to shut down the expression of specific proteins in the cell. The use of small RNAs for this purpose was thought to have successfully bypassed earlier problems associated with this technique, in particular, turning on the cell's anti-viral response pathway. Rather surprisingly, Bryan Williams and colleagues show that at least six different small RNAs that they tested turn on genes that are part of the interferon system, the cell's anti-viral response mechanism. Full activation of the interferon system would eventually lead to cell death. The authors do not study whether short RNAs also leads to extensive cell damage associated with the interferon response. The occurrence and extent of cell damage may depend on the amount of small RNAs added to cells.

Nonetheless, this study raises a cautionary note about the non-specific effects associated with this technology, and may have consequences for the future application of RNA interference.