Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis

Rinki Chauhan, Janani Ravi, Pratik Datta, Tianlong Chen, Dirk Schnappinger, Kevin E. Bassler, Gábor Balázsi () and Maria Laura Gennaro ()
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Rinki Chauhan: Public Health Research Institute, New Jersey Medical School, Rutgers University
Janani Ravi: Public Health Research Institute, New Jersey Medical School, Rutgers University
Pratik Datta: Public Health Research Institute, New Jersey Medical School, Rutgers University
Tianlong Chen: University of Houston
Dirk Schnappinger: Weill Cornell Medical College
Kevin E. Bassler: University of Houston
Gábor Balázsi: Stony Brook University
Maria Laura Gennaro: Public Health Research Institute, New Jersey Medical School, Rutgers University

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract 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 topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics.

Date: 2016
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DOI: 10.1038/ncomms11062

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