ArticleScientific reports2017
Cyclic di-GMP regulates Mycobacterium tuberculosis resistance to ethionamide.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 46 citations in OpenAlex.
- Cyclic di-GMP directly reprograms the multidrug resistance machinery via UspG-mediated sequestration of RamR in Klebsiella.PLoS pathogens · 2026Article
- Exploring the evolutionary divergence of cyclic di-nucleotide signaling in diverse mycobacterial species.Archives of microbiology · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Intracellular glutamine fluctuates with nitrogen availability and regulatesJournal of bacteriology · 2025Article
- Cyclic-di-GMP interferes with DNA-MucR-DNA bridging to derepress genes targeted by the xenogeneic silencer MucR.Nucleic acids research · 2025Article
- Crosstalk between cyclic-di-guanosine monophosphate and the sensor kinase MtrB regulates MtrA-dependent genes, bacterial growth, biofilm formation and lysosomal trafficking ofMicrobiology (Reading, England) · 2025Article
- Effects of mutations in multiple Ethionamide-resistance-associated genes amongFrontiers in cellular and infection microbiology · 2025Article
- Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis.Scientific reports · 2023Article
- Omics analysis of Mycobacterium tuberculosis isolates uncovers Rv3094c, an ethionamide metabolism-associated gene.Communications biology · 2023Article
- Crystal structure of oligoribonuclease from Vibrio cholerae O1 El Tor with bound peptide.Acta crystallographica. Section F, Structural biology communications · 2021Article
- A Comprehensive Evaluation of GeneLEAD VIII DNA Platform Combined to Deeplex Myc-TBFrontiers in cellular and infection microbiology · 2021Article
- Transcriptional portrait of M. bovis BCG during biofilm production shows genes differentially expressed during intercellular aggregation and substrate attachment.Scientific reports · 2020Article
- Transcriptional and Mycolic Acid Profiling inJournal of microbiology and biotechnology · 2020Article
- Fatty acylCoA synthetase FadD13 regulates proinflammatory cytokine secretion dependent on the NF-κB signalling pathway by binding to eEF1A1.Cellular microbiology · 2019Article
- A DNA-Binding Protein Tunes Septum Placement duringJournal of bacteriology · 2019Article
- Discovery of Two Native Baeyer-Villiger Monooxygenases for Asymmetric Synthesis of Bulky Chiral Sulfoxides.Applied and environmental microbiology · 2018Article
- Cyclic nucleotide signaling in Mycobacterium tuberculosis: an expanding repertoire.Pathogens and disease · 2018Article
- Systematic Identification ofMolecular & cellular proteomics : MCP · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberculosis is still on the top of infectious diseases list on both mobility and mortality, especially due to drug-resistance of Mycobacterium tuberculosis (M.tb). Ethionamide (ETH) is one of effective second line anti-TB drugs, a synthetic compound similar to isoniazid (INH) structurally, with existing severe problem of ETH resistance. ETH is a prodrug, which is activated by Etha inside M.tb, and etha is transcriptionally repressed by Ethr. We found that c-di-GMP could bind Ethr, enhanced the binding of Ethr to the promoter of etha, and then repressed the transcription of etha, thus caused resistance of M.tb to ETH. Through docking analysis and in vitro validation, we identified that c-di-GMP binds 3 amino acids of Ethr, i.e., Q125, R181 and E190, while the first 2 were the major binding sites. Homology analysis showed that Ethr was highly conservative among mycobacteria. Further docking analysis showed that c-di-GMP preferentially bound proteins of TetR family at the junction hole of symmetric dimer or tetramer proteins. Our results suggest a possible drug-resistance mechanism of ETH through the regulation of Ethr by c-di-GMP.
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Registered trials
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.