title: A novel copper-responsive regulon in Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: New York University School of Medicine, Department of Microbiology, 550 First Avenue MSB 236, New York, NY 10016, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Festa
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.forename: Susan
authors.initials: S
authors.lastname: Butler-Wu
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinsimer
authors.forename: Russell
authors.initials: R
authors.lastname: Gerads
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.forename: K Heran
authors.initials: KH
authors.lastname: Darwin
mesh_terms: D001665:Binding Sites; D003300:Copper / Q000378:metabolism*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D056426:Genetic Loci; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D018085:Regulon; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial; D003300:Copper