A novel copper‐responsive regulon in Mycobacterium tuberculosis

• Published in: Molecular microbiology Vol. 79; no. 1; pp. 133 - 148
• Main Authors: Festa, Richard A., Jones, Marcus B., Butler‐Wu, Susan, Sinsimer, Daniel, Gerads, Russell, Bishai, William R., Peterson, Scott N., Darwin, K. Heran
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2011; Blackwell
• Subjects: Bacteria; Bacteriology; Binding Sites; Biological and medical sciences; Copper; Copper - metabolism; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes; Genetic Loci; Homeostasis; Humans; Microbiology; Miscellaneous; Models, Biological; Molecular Sequence Data; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Mycobacterium tuberculosis - physiology; Promoter Regions, Genetic; Regulon; Sequence Analysis, DNA; Survival analysis; Regulon; Mycobacterium tuberculosis; Mycobacteriales; Mycobacteriaceae; Bacteria; Actinomycetes; Copper; Heavy metal
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2010.07431.x

Summary In this work we describe the identification of a copper‐inducible regulon in Mycobacterium tuberculosis (Mtb). Among the regulated genes was Rv0190/MT0200, a paralogue of the copper metalloregulatory repressor CsoR. The five‐locus regulon, which includes a gene that encodes the copper‐protective metallothionein MymT, was highly induced in wild‐type Mtb treated with copper, and highly expressed in an Rv0190/MT0200 mutant. Importantly, the Rv0190/MT0200 mutant was hyper‐resistant to copper. The promoters of all five loci share a palindromic motif that was recognized by the gene product of Rv0190/MT0200. For this reason we named Rv0190/MT0200 RicR for regulated in copper repressor. Intriguingly, several of the RicR‐regulated genes, including MymT, are unique to pathogenic Mycobacteria. The identification of a copper‐responsive regulon specific to virulent mycobacterial species suggests copper homeostasis must be maintained during an infection. Alternatively, copper may provide a cue for the expression of genes unrelated to metal homeostasis, but nonetheless necessary for survival in a host.