title: The promoter of Rv0560c is induced by salicylate and structurally-related compounds in Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a major global health threat. During infection, bacteria are believed to encounter adverse conditions such as iron depletion. Mycobacteria synthesize iron-sequestering mycobactins, which are essential for survival in the host, via the intermediate salicylate. Salicylate is a ubiquitous compound which is known to induce a mild antibiotic resistance phenotype. In M. tuberculosis salicylate highly induces the expression of Rv0560c, a putative methyltransferase. We identified and characterized the promoter and regulatory elements of Rv0560c. P(Rv0560c) activity was highly inducible by salicylate in a dose-dependent manner. The induction kinetics of P(Rv0560c) were slow, taking several days to reach maximal activity, which was sustained over several weeks. Promoter activity could also be induced by compounds structurally related to salicylate, such as aspirin or para-aminosalicylic acid, but not by benzoate, indicating that induction is specific to a structural motif. The -10 and -35 promoter elements were identified and residues involved in regulation of promoter activity were identified in close proximity to an inverted repeat spanning the -35 promoter element. We conclude that Rv0560c expression is controlled by a yet unknown repressor via a highly-inducible promoter.
authors.affiliation: Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Dorothée L
authors.initials: DL
authors.lastname: Schuessler
authors.forename: Tanya
authors.initials: T
authors.lastname: Parish
mesh_terms: D000595:Amino Acid Sequence; D020240:Apraxia, Ideomotor; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D016384:Consensus Sequence; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D000090463:Iron Deficiencies; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012459:Salicylates / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D012459:Salicylates; D001616:beta-Galactosidase