<i>Mycobacterium tuberculosis</i>Sigma Factor E Regulon Modulates the Host Inflammatory Response

Abstract

Mycobacterium tuberculosis survives in macrophages and usually subverts the bactericidal mechanisms of these phagocytes. The understanding of this host-pathogen interaction is relevant for the development of new treat-ments for tuberculosis. The adaptation ofM. tuberculosis to intracellular life depends on its ability to regulate the expression of its genes. Sigma factors are important bacterial transcription activators that bind to the RNA poly-merase andgive it promoter specificity. Sigma factorE (SigE) controls the expressionof genes that are essential for virulence. We have identified the SigE regulon during infection of macrophages, and we analyzed the impact of this regulon on the transcriptional response of phagocytes. Our results indicate that SigE regulates the expression of genes involved in the maintenance ofM. tuberculosis cell envelope integrity and function during macrophage infection. Analysis of the phagocytes ’ transcriptional response indicates that the SigE regulon is involved in the modulation of the inflammatory response. Tuberculosis remains one of the major public health challenges in the world, despite more than a century of effort to combat the disease. The ability of Mycobacte-rium tuberculosis to overcome the bactericidal action of macrophages is a characteristic that contributes to the