A novel copper-responsive regulon in Mycobacterium tuberculosis

Richard A. Festa, Marcus B. Jones, Susan Butler-Wu, Daniel Sinsimer, Russell Gerads, William R. Bishai, Scott N. Peterson, K. Heran Darwin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)133-148
Number of pages16
JournalMolecular Microbiology
Volume79
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Festa, R. A., Jones, M. B., Butler-Wu, S., Sinsimer, D., Gerads, R., Bishai, W. R., Peterson, S. N., & Darwin, K. H. (2011). A novel copper-responsive regulon in Mycobacterium tuberculosis. Molecular Microbiology, 79(1), 133-148. https://doi.org/10.1111/j.1365-2958.2010.07431.x