Techniques and Applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.

In the field of tuberculosis, the challenge is to interpret genome information in the context of the host–pathogen interaction, and then translate the resulting knowledge into a new generation of drugs and vaccines with which to arm ourselves in the fight against this ancient disease. Structural genomics, the large-scale determination of protein structures, promises to provide many useful data for drug discovery. To date, 38 protein structures have been determined from Mycobacterium tuberculosis. Most are those of proteins involved in intermediary metabolism and lipid metabolism. These structures will provide the opportunity to undertake structure-guided drug discovery programs in the search for new classes of antibiotics. Existing information will provide spin-offs for future applications, but the way ahead is still arduous because it is difficult to obtain sufficient yields of the functionally active gene products, despite numerous efforts to optimize the prokaryotic expression systems. More protein candidates, responsible for virulence, intracellular survival, transcriptional regulation or drug resistance, must be characterized to develop new treatments for tuberculosis.