A novel copper-responsive regulon in Mycobacterium tuberculosis

Mol Microbiol. 2011 Jan;79(1):133-48. doi: 10.1111/j.1365-2958.2010.07431.x. Epub 2010 Oct 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Copper / metabolism*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Genetic Loci
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism
  • Mycobacterium tuberculosis / physiology*
  • Promoter Regions, Genetic
  • Regulon*
  • Sequence Analysis, DNA

Substances

  • DNA, Bacterial
  • Copper

Associated data

  • GENBANK/GU726749