**Author details**

DosS/DosT-DosR was previously described, and responds to initial hypoxic stress (Table 1.) (Park et al, 2003). Some of the genes controlled by the transcriptional regulator DosR are upregulated by hypoxic stress, and are also part of the transcriptional regulator PhoP regulon, a member of the PhoP/R two component system. While it is unknown what environmental signal PhoP or the sensor kinase PhoR are responding to, genes controlled by PhoP either directly or indirectly are upregulated by such stresses as acidity and low oxygen (Table 1.)

Mycobacterial RNA polymerase catalyzes RNA synthesis from specific promoter sequences. This RNA polymerase is composed of subunits that comprise the core holoenzyme, and include two α subunits, a β, a β' and a ω subunit. The core enzyme, however, cannot target specific promoter sequences. A sigma factor is required for this function, and can bind and recognize specific -10 and -35 promoter sequences. As the mycobacterial genome possesses many different sigma factors, these RNA polymerase components can recognize diverse mycobacterial promoter sequences to activate a whole class of genes. This activity is in addition to specific transcription factors which bind to promoters, regulate transcription, and are not

The mycobacterial genome possesses many different sigma factors that belong to different categories. The *M. tuberculosis* σA is responsible for regulating housekeeping genes, and is also an essential gene for mycobacterial growth *in vitro* and *in vivo*. While the sigma factor σ<sup>B</sup> is highly similar to σA, it is nonessential and is induced by a variety of stresses including oxidative stress, heat shock, cold shock, stationary phase, and low aeration (Lee et al, 2008). There are a number of sigma factors designated to have extracellular function, and some respond to environmental stresses and are involved in the synthesis of the mycobacterial envelope. These sigma factors are SigC, SigE, SigF, SigG, SigH, SigI, SigJ, SigK, SigL, and SigM. One sigma factor that is known to respond to nutrient starvation is SigF. The sigma factor SigE is involved in response to heat shock and SDS exposure (Manganelli et al, 2004). Both SigJ and SigF are induced in response to antibiotic exposure (Manganelli et al, 2004). The sigma factor SigH also responds to heat shock and oxidative stress (Manganelli et al, 2004). Thus the use of sigma factors by the mycobacterial cell is a manner in which "master regulators" can control whole classes of genes to rapidly facilitate gene regulation in response to specific environmental

As mycobacteria invade their human hosts they must respond to a plethora of stresses many of which are generated by the host's immune system. Under this selective pressure, *M. tuberculosis* has evolved mechanisms to combat the toxic insults of the host. Although myco‐

(Gonzalo-Asensio et al, 2008).

12 Tuberculosis - Current Issues in Diagnosis and Management

part of the RNA polymerase enzyme.

**13. Sigma factors**

stresses (Table 1.).

**14. Summary**

#### Beatrice Saviola

Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona CA, USA
