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.
Highlights
Mycobacteria inhabit diverse niches and display high metabolic versatility
The conservation of the KstR regulators in M. avium subspecies paratuberculosis suggests that cholesterol catabolism is important for this intestinal pathogen. This is supported by the recent observation that cholesterol is a carbon source for M. avium subspecies paratuberculosis in the bovine intestine [21]. Conservation analysis identifies those TetR family of transcriptional regulators (TFTRs) that are only present in the pathogenic representatives In order to identify those TFTRs that might be uniquely involved in pathogenic processes we identified those TFTRs that were missing from both M. smegmatis and M. gilvum but present in the pathogenic species (Additional file 2: Table S2)
In this work we have shown that the TFTRs are the most abundant family of transcriptional regulators with 906 TFTRs across the 10 species examined
Summary
Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are able to survive in the environment. TetR family transcriptional regulators (TFTRs) are common one-component prokaryotic signal transduction systems. This family of regulators contain a conserved helix turn helix (HTH) motif at the N-terminal DNAbinding end of the protein and a ligand binding pocket at the C-terminal end. The paradigm was first described in Escherichia coli and TetR, the founding member of the family, is a repressor that controls the expression of a divergently oriented efflux pump that transports tetracycline out of the cell [2]. TFTRs are best known to bind small molecule ligands to control divergently oriented efflux pumps and, in addition to E. coli TetR, there are several good model systems including Staphylococcus aureus QacR [3]
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