A novel copper‐responsive regulon in Mycobacterium tuberculosis
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‐protec...
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Published in | Molecular microbiology Vol. 79; no. 1; pp. 133 - 148 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.01.2011
Blackwell |
Subjects | |
Online Access | Get full text |
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Abstract | 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. |
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AbstractList | 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. 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. 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 ABSTRACT] 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. |
Author | Gerads, Russell Peterson, Scott N. Bishai, William R. Darwin, K. Heran Jones, Marcus B. Butler‐Wu, Susan Festa, Richard A. Sinsimer, Daniel |
AuthorAffiliation | 6 Johns Hopkins School of Medicine, Department of Medicine, Division of Infectious Diseases, 1550 Orleans St. Room 108, Baltimore, MD 21231 USA 1 New York University School of Medicine, Department of Microbiology, 550 First Avenue MSB 236, New York, NY 10016 USA 5 Applied Speciation and Consulting, LLC, 18804 Northcreek Parkway, Bothell, WA 98011 USA 2 Pathogen Genomics Resource Center (PFGRC), J. Craig Venter Institute (JCVI), 9704 Medical Center Drive, Rockville, MD 20850 USA |
AuthorAffiliation_xml | – name: 6 Johns Hopkins School of Medicine, Department of Medicine, Division of Infectious Diseases, 1550 Orleans St. Room 108, Baltimore, MD 21231 USA – name: 1 New York University School of Medicine, Department of Microbiology, 550 First Avenue MSB 236, New York, NY 10016 USA – name: 5 Applied Speciation and Consulting, LLC, 18804 Northcreek Parkway, Bothell, WA 98011 USA – name: 2 Pathogen Genomics Resource Center (PFGRC), J. Craig Venter Institute (JCVI), 9704 Medical Center Drive, Rockville, MD 20850 USA |
Author_xml | – sequence: 1 givenname: Richard A. surname: Festa fullname: Festa, Richard A. – sequence: 2 givenname: Marcus B. surname: Jones fullname: Jones, Marcus B. – sequence: 3 givenname: Susan surname: Butler‐Wu fullname: Butler‐Wu, Susan – sequence: 4 givenname: Daniel surname: Sinsimer fullname: Sinsimer, Daniel – sequence: 5 givenname: Russell surname: Gerads fullname: Gerads, Russell – sequence: 6 givenname: William R. surname: Bishai fullname: Bishai, William R. – sequence: 7 givenname: Scott N. surname: Peterson fullname: Peterson, Scott N. – sequence: 8 givenname: K. Heran surname: Darwin fullname: Darwin, K. Heran |
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Keywords | Regulon Mycobacterium tuberculosis Mycobacteriales Mycobacteriaceae Bacteria Actinomycetes Copper Heavy metal |
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Notes | Present addresses: University of Washington Medical Center, Clinical Microbiology Laboratory, 1959 NE Pacific Street, NW120, Seattle, WA 98195‐7110, USA University of Medicine and Dentistry of New Jersey‐Robert Wood Johnson Medical School, Child Health Institute of New Jersey, 89 French Street, 4th Floor, New Brunswick, NJ 08901, USA. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Child Health Institute of New Jersey, 89 French Street, 4th Floor, New Brunswick, NJ 08901 USA Current address: University of Washington Medical Center, Clinical Microbiology Laboratory, 1959 NE Pacific Street, NW120, Seattle, WA 98195-7110 USA |
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In this work we describe the identification of a copper‐inducible regulon in Mycobacterium tuberculosis (Mtb). Among the regulated genes was... In this work we describe the identification of a copper-inducible regulon in Mycobacterium tuberculosis (Mtb). Among the regulated genes was Rv0190/MT0200, a... In this work we describe the identification of a copper‐inducible regulon in Mycobacterium tuberculosis ( Mtb ). Among the regulated genes was Rv0190/MT0200, a... In this work we describe the identification of a copper-inducible regulon in Mycobacterium tuberculosis ( Mtb ). Among the regulated genes was Rv0190/MT0200, a... |
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SubjectTerms | 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 |
Title | A novel copper‐responsive regulon in Mycobacterium tuberculosis |
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