ArticleBMC microbiology2014
DevR (DosR) mimetic peptides impair transcriptional regulation and survival of Mycobacterium tuberculosis under hypoxia by inhibiting the autokinase activity of DevS sensor kinase.
Article in BMC microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Cefpiramide RestrictsACS medicinal chemistry letters · 2026Article
- Harnessing Natural Product Compounds to Target Dormancy Survival Regulator (DosR) in Latent Tuberculosis Infection (LTBI): An In Silico Strategy Against Dormancy.Advances in respiratory medicine · 2025Article
- Harnessing hypoxia: bacterial adaptation and chronic infection in cystic fibrosis.FEMS microbiology reviews · 2025Review
- Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.Current issues in molecular biology · 2024Review
- Two-component sensor histidine kinases of Mycobacterium tuberculosis: Beacons for niche navigation.Molecular microbiology · 2022Review
- Targeting of Regulators as a Promising Approach in the Search for Novel Antimicrobial Agents.Microorganisms · 2022Article
- Progress Overview of Bacterial Two-Component Regulatory Systems as Potential Targets for Antimicrobial Chemotherapy.Antibiotics (Basel, Switzerland) · 2020Review
- 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
- Impact of Hypoxia on Drug Resistance and Growth Characteristics of Mycobacterium tuberculosis Clinical Isolates.PloS one · 2016Article
- Article
- Structural insights into HetR-PatS interaction involved in cyanobacterial pattern formation.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTwo-component systems have emerged as compelling targets for antibacterial drug design for a number of reasons including the distinct histidine phosphorylation property of their constituent sensor kinases. The DevR-DevS/DosT two component system of Mycobacterium tuberculosis (M. tb) is essential for survival under hypoxia, a stress associated with dormancy development in vivo. In the present study a combinatorial peptide phage display library was screened for DevS histidine kinase interacting peptides with the aim of isolating inhibitors of DevR-DevS signaling.
resultsDevS binding peptides were identified from a phage display library after three rounds of panning using DevS as bait. The peptides showed sequence similarity with conserved residues in the N-terminal domain of DevR and suggested that they may represent interacting surfaces between DevS and DevR. Two DevR mimetic peptides were found to specifically inhibit DevR-dependent transcriptional activity and restrict the hypoxic survival of M. tb. The mechanism of peptide action is majorly attributed to an inhibition of DevS autokinase activity.
conclusionsThese findings demonstrate that DevR mimetic peptides impede DevS activation and that intercepting DevS activation at an early step in the signaling cascade impairs M. tb survival in a hypoxia persistence model.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.