Activation of signaling cascades is critical for Mycobacterium tuberculosis (Mtb) to adapt the macrophage lifestyle. Parallel to several signal systems, sigma factor systems, especially the extra-cytoplasmic function sigma factors, are crucial for Mtb signaling. Most sigma factors lack a signal sensory domain and often are activated by various proteins that perceive the environmental cues and relay the signals through variegated post-translational modifications via the activity of antisigma factor, protein kinase and related transcriptional regulators. Antisigma factors are further controlled by multiple mechanisms. SigK senses the environmental redox state directly. Phosphorylation and lysine acetylation added another dimension to the regulatory hierarchy. This review will provide insights into Mtb pathogenesis, and lay the foundation for the discovery of novel approaches for therapeutic interventions.
Keywords: Mycobacterium tuberculosis; post-translational regulation; sigma factor.