title: The MarR family transcription factor Rv1404 coordinates adaptation of Mycobacterium tuberculosis to acid stress via controlled expression of Rv1405c, a virulence-associated methyltransferase.
abstract: Coordinated regulation of gene expression is essential for pathogen adaptation in vivo. Understanding the control of these virulence circuits in the TB pathogen Mycobacterium tuberculosis is a key challenge if we are to increase our basic understanding of how this organism establishes infection. In this study we focused on the transcriptional regulator Rv1404 that shows similarity to the MarR family of transcriptional repressors. Rv1404 derepresses a set of genes in vivo that have been implicated in virulence and may therefore allow adaptation of M. tuberculosis to the intracellular environment. We used a combination of ChIP-qPCR and Electromobility Band Shift Assays (EMSA) to show that Rv1404 coordinates gene expression in response to stresses such as low pH in M. tuberculosis. Two genes regulated by Rv1404, rv1403c and rv1405c, encode putative SAM-dependent methyltransferases. To elucidate gene function, M. tuberculosis rv1403c and rv1405c mutants were constructed. The mutants showed attenuated growth in response to in vitro stress conditions that mimic the intracellular milieu. Our data sheds new light on the function of a novel regulon controlled by Rv1404 that coordinates adaptation of M. tuberculosis to the in vivo environment and reveals the Rv1405c and Rv1403c methyltransferases as playing a role in this adaptive process.
authors.affiliation: School of Veterinary Medicine, University College Dublin, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: Healy
authors.affiliation: Animal Health and Veterinary Laboratories Agency Weybridge, Surrey KT15 3NB, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Golby
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Ireland; School of Agriculture and Food Science, University College Dublin, Ireland.
authors.forename: David E
authors.initials: DE
authors.lastname: MacHugh
authors.affiliation: School of Veterinary Medicine, University College Dublin, Ireland; UCD Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Ireland; School of Medicine, University College Dublin, Ireland; School of Biomolecular and Biomedical Sciences, University College Dublin, Ireland. Electronic address: stephen.gordon@ucd.ie.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Gordon
mesh_terms: D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial; D005838:Genotype; D054884:Host-Pathogen Interactions; D006863:Hydrogen-Ion Concentration; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C567945:MarR-family transcriptional regulatory protein, Mycobacterium; D014157:Transcription Factors; D008780:Methyltransferases
keywords: Acid stress; Mycobacteriun tuberculosis; Transcriptional regulation; Virulence