ArticleCell chemical biology2022
An allosteric inhibitor of bacterial Hsp70 chaperone potentiates antibiotics and mitigates resistance.
Article in Cell chemical biology, 2022. 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, 34 citations in OpenAlex.
- A Small Molecule Substrate Mimic to Inhibit Bacterial Hsp70 Chaperone Function.Chembiochem : a European journal of chemical biology · 2026Article
- Microbial Natural Products Targeting theMicroorganisms · 2026Review
- Direct single-molecule visualization of Hsp90-mediated relief of an Hsp70-folding block.Science advances · 2026Article
- Function-specific epistasis shapes evolutionary trajectories towards antibiotic resistance.Nature communications · 2026Article
- These 'master' proteins protect us from deadly mutations - and could inspire new drugs.Nature · 2026Article
- Article
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- Exploring allosteric efflux pump inhibitors and the role of bacterial membrane potential in modulating drug resistance.Frontiers in microbiology · 2026Review
- Secreted proteins ofFrontiers in tuberculosis · 2026Review
- A lignan compound regulates LPS modifications via PmrA/B signaling cascades to potentiate colistin efficacy in vivo.PLoS pathogens · 2025Article
- New Structure Activity Relationship Insight into the Role of the C-3 Extension on Rifamycin Antimycobacterial Activity.ChemMedChem · 2025Article
- Preferential binding of ADP-bound mitochondrial HSP70 to the nucleotide exchange factor GRPEL1 over GRPEL2.Protein science : a publication of the Protein Society · 2024Article
- Mycoplasma DnaK expression increases cancer development in vivo upon DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structure of the M. tuberculosis DnaK-GrpE complex reveals how key DnaK roles are controlled.Nature communications · 2024Article
- Novel target and cofactor repertoire for the transcriptional regulator JTY_0672 fromFrontiers in microbiology · 2024Article
- New antibacterial candidates against Acinetobacter baumannii discovered by in silico-driven chemogenomics repurposing.PloS one · 2024Article
- Peptide-based molecules for the disruption of bacterial Hsp70 chaperones.Current opinion in chemical biology · 2023Review
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- Selection of Multi-Drug Targets against Drug-ResistantInternational journal of molecular sciences · 2023Article
- Optimized Microscale Protein Aggregation Suppression Assay: A Method for Evaluating the Holdase Activity of Chaperones.Methods in molecular biology (Clifton, N.J.) · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
DnaK is the bacterial homolog of Hsp70, an ATP-dependent chaperone that helps cofactor proteins to catalyze nascent protein folding and salvage misfolded proteins. In the pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), DnaK and its cofactors are proposed antimycobacterial targets, yet few small-molecule inhibitors or probes exist for these families of proteins. Here, we describe the repurposing of a drug called telaprevir that is able to allosterically inhibit the ATPase activity of DnaK and to prevent chaperone function by mimicking peptide substrates. In mycobacterial cells, telaprevir disrupts DnaK- and cofactor-mediated cellular proteostasis, resulting in enhanced efficacy of aminoglycoside antibiotics and reduced resistance to the frontline TB drug rifampin. Hence, this work contributes to a small but growing collection of protein chaperone inhibitors, and it demonstrates that these molecules disrupt bacterial mechanisms of survival in the presence of different antibiotic classes.
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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.