Mycobacterium tuberculosis Sigma Factor E Regulon Modulates the Host Inflammatory Response

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 treatmentsfortuberculosis.TheadaptationofM.tuberculosistointracellularlifedependsonitsabilitytoregulatethe expression of its genes. Sigma factors are important bacterial transcription activators that bind to the RNA polymeraseandgiveitpromoterspecificity.SigmafactorE(SigE)controlstheexpressionofgenesthatareessentialfor virulence. We have identified the SigE regulon during infection of macrophages, and we analyzed the impact of thisregulononthetranscriptionalresponseofphagocytes.OurresultsindicatethatSigEregulatestheexpression of genes involved in the maintenance of M. 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 Mycobacterium tuberculosis to overcome the bactericidal action of macrophages is a characteristic that contributes to the successofthismicroorganismasahumanpathogen.For this reason, studies leading to a better understanding of this intriguing macrophage-pathogen interaction can help to develop improved intervention strategies to prevent or cure tuberculosis. Among the most important bacterial transcription activators are the sigma factors. By binding to the RNA polymerase,sigmafactorsprovidethespecificityforpar