biostudies-literatureChauhan RNIAID NIH HHSNHLBI NIH HHSNIGMS NIH HHS11062https://www.ebi.ac.uk/biostudies/studies/S-EPMC4821874biostudies-literatureUnknown7Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topologicaNature communicationsReconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis.PMC4821874R21 AI095924GM096189R01 GM096189HL106788AI095924R01 HL106788Chauhan RDatta PSchnappinger DGennaro MLRavi JBalazsi GChen TBassler KEfalseReconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis.Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topologica2016-01-01T00:00:00Z2016 Mar2025-04-26T02:15:49.314Z2019-03-27T03:11:16ZS-EPMC48218742702951510.1038/ncomms11062