A novel copper-responsive regulon in Mycobacterium tuberculosis
Richard A Festa1, Marcus B Jones, Susan Butler-Wu
1New York University School of Medicine, Department of Microbiology, 550 First Avenue MSB 236, New York, NY 10016, USA.
Molecular Microbiology
|December 21, 2010
Summary
Researchers identified a copper-inducible regulon in Mycobacterium tuberculosis (Mtb), controlled by a new repressor named RicR. This discovery reveals how Mtb manages copper, potentially impacting its survival within hosts.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Copper is essential for bacterial physiology but toxic at high concentrations.
- Mycobacterium tuberculosis (Mtb) requires mechanisms to regulate copper homeostasis.
- Metalloregulatory proteins play a crucial role in controlling gene expression in response to metal ions.
Purpose of the Study:
- To identify and characterize copper-inducible genes in Mycobacterium tuberculosis.
- To elucidate the regulatory mechanisms governing copper resistance in Mtb.
- To discover novel copper-responsive pathways specific to pathogenic mycobacteria.
Main Methods:
- Gene expression analysis in wild-type and mutant Mtb strains.
- Identification of DNA-binding motifs recognized by regulatory proteins.
- Construction and characterization of a mutant lacking the Rv0190/MT0200 gene.
- Copper resistance assays.
Main Results:
- A five-locus copper-inducible regulon was identified in Mtb.
- Rv0190/MT0200, named RicR (regulated in copper repressor), was identified as a copper-responsive transcriptional repressor.
- The Rv0190/MT0200 mutant exhibited hyper-resistance to copper.
- A conserved palindromic motif recognized by RicR was found in the promoters of the regulated genes.
- RicR regulates the expression of MymT, a copper-protective metallothionein.
Conclusions:
- RicR controls a specific copper-inducible regulon in Mtb, including genes essential for copper resistance.
- The identified regulon and its regulator RicR are specific to pathogenic mycobacteria, suggesting a role in host-pathogen interactions.
- Copper homeostasis is critical for Mtb survival during infection, or copper may act as a signaling molecule for virulence gene expression.
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