Session 1C: Inaugural Lectures by Fellows/Associates

Cellular Redox Poise In M. Tuberculosis Is Modulated By A Novel Actinomycetes-specific Transcription Factor

Mycobacterium tuberculosis (Mtb) has evolved multifarious cellular processes in response to the myriad of stresses it encounters within the host. Towards dissecting the molecular mechanisms utilized by the pathogen, we explored TnSeq data, to identify transcription factors (TFs) that are essential for the pathogen’s survival within the host. A single TF – Rv1332 (AosR) uncharacterized across actinomycetes was thus identified. Our data indicates that oxidative stress alters the conformation of AosR through the formation of a single intrasubunit disulphide bond, which in turn facilitates its interaction with an extracytoplasmic sigma factor, SigH. This leads to the specific upregulation of the CysMdependent actinomycetes-specific non-canonical cysteine biosynthesis pathway through an auxiliary intragenic stress-responsive promoter, an axis critical in detoxifying host-derived oxidative radicals. The results of our study unearth new facets of the Mtb–host relationship and underscore the novel mechanisms this pathogen has evolved to get the better of its hostile host.