ArticleThe Journal of biological chemistry2015
Mycobacterium tuberculosis response regulators, DevR and NarL, interact in vivo and co-regulate gene expression during aerobic nitrate metabolism.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- Cefpiramide RestrictsACS medicinal chemistry letters · 2026Article
- Multiple input-multiple output (MIMO) designs in two-component signalling systems of Mycobacterium tuberculosis.FEMS microbiology reviews · 2026Review
- Characterization of two co-regulated response regulators inJournal of bacteriology · 2025Article
- Mycobacterial MutT1-mediated dephosphorylation of the sensor histidine kinases reveals a new link in the regulation of the two-component signaling.Nucleic acids research · 2025Article
- Comparison of the transcriptome, lipidome, and c-di-GMP production between BCGΔBCG1419c and BCG, with Mincle- and Myd88-dependent induction of proinflammatory cytokines in murine macrophages.Scientific reports · 2024Article
- Regulatory Intersection of Two-component System and Ser/Thr Protein Kinase Signaling in Mycobacterium tuberculosis.Journal of molecular biology · 2024Article
- Novel target and cofactor repertoire for the transcriptional regulator JTY_0672 fromFrontiers in microbiology · 2024Article
- Dual functioning by the PhoR sensor is a key determinant to Mycobacterium tuberculosis virulence.PLoS genetics · 2023Article
- Article
- The Effects of Paroxetine on Benthic Microbial Food Web and Nitrogen Transformation in River Sediments.International journal of environmental research and public health · 2022Article
- Hit Compounds and Associated Targets in IntracellularMolecules (Basel, Switzerland) · 2022Article
- Two-component sensor histidine kinases of Mycobacterium tuberculosis: Beacons for niche navigation.Molecular microbiology · 2022Review
- Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity.International journal of molecular sciences · 2021Review
- Transcriptional and Post-transcriptional Control of the Nitrate Respiration in Bacteria.Frontiers in molecular biosciences · 2021Review
- Review
- Potential therapeutic approaches for a sleeping pathogen: tuberculosis a case for bioinorganic chemistry.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Review
- Inhibiting DosRST as a new approach to tuberculosis therapy.Future medicinal chemistry · 2020Review
- Comparative transcriptomics reveals PrrAB-mediated control of metabolic, respiration, energy-generating, and dormancy pathways in Mycobacterium smegmatis.BMC genomics · 2019Article
- Article
- Interplay of PhoP and DevR response regulators defines expression of the dormancy regulon in virulentThe Journal of biological chemistry · 2018Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis genes Rv0844c/Rv0845 encoding the NarL response regulator and NarS histidine kinase are hypothesized to constitute a two-component system involved in the regulation of nitrate metabolism. However, there is no experimental evidence to support this. In this study, we established M. tuberculosis NarL/NarS as a functional two-component system and identified His(241) and Asp(61) as conserved phosphorylation sites in NarS and NarL, respectively. Transcriptional profiling between M. tuberculosis H37Rv and a ΔnarL mutant strain during exponential growth in broth cultures with or without nitrate defined an ∼30-gene NarL regulon that exhibited significant overlap with DevR-regulated genes, thereby implicating a role for the DevR response regulator in the regulation of nitrate metabolism. Notably, expression analysis of a subset of genes common to NarL and DevR regulons in M. tuberculosis ΔdevR, ΔdevSΔdosT, and ΔnarL mutant strains revealed that in response to nitrite produced during aerobic nitrate metabolism, the DevRS/DosT regulatory system plays a primary role that is augmented by NarL. Specifically, NarL itself was unable to bind to the narK2, acg, and Rv3130c promoters in phosphorylated or unphosphorylated form; however, its interaction with DevR∼P resulted in cooperative binding, thereby enabling co-regulation of these genes. These findings support the role of physiologically derived nitrite as a metabolic signal in mycobacteria. We propose NarL-DevR binding, possibly as a heterodimer, as a novel mechanism for co-regulation of gene expression by the DevRS/DosT and NarL/NarS regulatory systems.
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