Sigma Factors: Key Molecules in Mycobacterium tuberculosis Physiology and Virulence

Rapid adaptation to changing environments is one of the keys to the success of microorganisms. Since infection is a dynamic process, it is possible to predict that Mycobacterium tuberculosis adaptation involves continuous modulation of its global transcriptional profile in response to the changing environment found in the human body. In the last 18 years several studies have stressed the role of sigma (s) factors in this process. These are small interchangeable subunits of the RNA polymerase holoenzyme that are required for transcriptional initiation and that determine promoter specificity. The M. tuberculosis genome encodes 13 of these proteins, one of which-the principal s factor s A-is essential. Of the other 12 s factors, at least 6 are required for virulence. In this article we review our current knowledge of mycobacterial s factors, their regulons, the complex mechanisms determining their regulation, and their roles in M. tuberculosis physiology and virulence.