Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

Abstract

BackgroundMycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria.ResultsWe used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs.ConclusionThis study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users.

Resistance to Thiacetazone Derivatives Active against Mycobacterium abscessus Involves Mutations in the MmpL5 Transcriptional Repressor MAB_4384

“…Subsequent PCR/ sequencing unraveled mutations in this gene in all 11 D15-resistant strains. MAB_4384 belongs to the family of TetR regulators, which represents the most abundant family of HTH regulators in mycobacteria, making up 26% to 48% of the HTH DNAbinding capacity in mycobacterial species with large numbers found essentially in the soil-dwelling species (44). In agreement with the general assumption that approximately 60% of the TetR regulators are divergently oriented with their neighbor, MAB_4384 was found in the opposite orientation relative to its mmpS5-mmpL5 target genes.…”

Path‐seq identifies an essential mycolate remodeling program for mycobacterial host adaptation

“…The EGRIN model predicted regulation of module 276 by a TetR‐type TF, Rv0472c, with homologs across all mycobacteria, including M. leprae (Balhana et al , ). When overexpressed in MTB, Rv0472c led to significant repression of 15 genes, but only desA1 and desA2 had significant binding of Rv0472c in their promoter region from ChIP‐seq analysis (Minch et al , ; Data ref: Minch et al , ).…”

“…Interestingly, all of the PDIM-related genes of module 276 genes (ppsD/E, drrABC, papA5) were identified in a highcontent imaging analysis of bacterial mutants during macrophage infection (Barczak et al, 2017). More specifically, they found mutants of these genes impaired intracellular survival and reduced type I interferon (IFN) response in host cells (Barczak et al, 2017 (Balhana et al, 2015). When overexpressed in MTB, Rv0472c led to significant repression of 15 genes, but only desA1 and desA2 had significant binding of Rv0472c in their promoter region from ChIP-seq analysis Data ref: Minch et al, 2015).…”

The Structure of the Transcriptional Repressor KstR in Complex with CoA Thioester Cholesterol Metabolites Sheds Light on the Regulation of Cholesterol Catabolism in Mycobacterium tuberculosis

“…TFRs, which are the most abundant family of transcriptional regulators in mycobacteria and other actinomycetes (45), make up a large and structurally variable group of proteins, especially in their LBDs, which have evolved to accommodate a wide variety of ligands. The evolution of ligand-specific binding has progressed in parallel with the allosteric mechanisms that govern protein activity.…”