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A novel copper‐responsive regulon in Mycobacterium tuberculosis
Author(s) -
Festa Richard A.,
Jones Marcus B.,
ButlerWu Susan,
Sinsimer Daniel,
Gerads Russell,
Bishai William R.,
Peterson Scott N.,
Darwin K. Heran
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2010.07431.x
Subject(s) - regulon , biology , gene , mutant , mycobacterium tuberculosis , genetics , repressor , locus (genetics) , virulence , mycobacterium tuberculosis complex , microbiology and biotechnology , promoter , tuberculosis , gene expression , medicine , pathology
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 r egulated i n c opper r epressor. 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.