title: Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions.
abstract: BACKGROUND
  Mycobacteria 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Royal College street, Camden, London, NW1 OTU, UK. r.balhana@surrey.ac.uk.|Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Stag Hill, Guildford, GU2 7XH, UK. r.balhana@surrey.ac.uk.
authors.forename: Ricardo J C
authors.initials: RJ
authors.lastname: Balhana
authors.affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Royal College street, Camden, London, NW1 OTU, UK. ashima@iitk.ac.in.|Indian Institute of Technology Kanpur, Kanpur, India. ashima@iitk.ac.in.
authors.forename: Ashima
authors.initials: A
authors.lastname: Singla
authors.affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Royal College street, Camden, London, NW1 OTU, UK. drmsikder@bau.edu.bd.|Department of Pharmacology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh. drmsikder@bau.edu.bd.
authors.forename: Mahmudul Hasan
authors.initials: MH
authors.lastname: Sikder
authors.affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Royal College street, Camden, London, NW1 OTU, UK. mwithers@rvc.ac.uk.
authors.forename: Mike
authors.initials: M
authors.lastname: Withers
authors.affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Royal College street, Camden, London, NW1 OTU, UK. skendall@rvc.ac.uk.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Kendall
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D008024:Ligands; D009161:Mycobacterium / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D008024:Ligands