ArticleMolecular microbiology2018
In silico discovery of small molecules that inhibit RfaH recruitment to RNA polymerase.
Article in Molecular microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed.
- A review on hypervirulent and multidrug-resistant Klebsiella pneumoniae: An emerging threat to human health.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Exploration of the structural and functional diversity in the metamorphic RfaH subfamily.bioRxiv : the preprint server for biology · 2026Article
- Synergistic effect of the rifaximin-berberine combination againstBiomolecules & biomedicine · 2026Article
- Discovering novel inhibitors of RfaH from Klebsiella pneumoniae to combat antimicrobial resistance.Archives of microbiology · 2024Article
- Evaluation of Antimicrobial Activities against VariousMolecules (Basel, Switzerland) · 2023Article
- A computational framework for identifying chemical compounds to bind Apolipoprotein E4 for Alzheimer's disease intervention.Frontiers in systems biology · 2023Article
- Metamorphic proteins under a computational microscope: Lessons from a fold-switching RfaH protein.Computational and structural biotechnology journal · 2022Review
- Virulence Factors in HypervirulentFrontiers in microbiology · 2021Review
- Article
- Differential Local Stability Governs the Metamorphic Fold Switch of Bacterial Virulence Factor RfaH.Biophysical journal · 2020Article
- NusG, an Ancient Yet Rapidly Evolving Transcription Factor.Frontiers in microbiology · 2020Review
- Identification of Four Amoebicidal Nontoxic Compounds by a Molecular Docking Screen ofACS infectious diseases · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
RfaH is required for virulence in several Gram-negative pathogens including Escherichia coli and Klebsiella pneumoniae. Through direct interactions with RNA polymerase (RNAP) and ribosome, RfaH activates the expression of capsule, cell wall and pilus biosynthesis operons by reducing transcription termination and activating translation. While E. coli RfaH has been extensively studied using structural and biochemical approaches, limited data are available for other RfaH homologs. Here we set out to identify small molecule inhibitors of E. coli and K. pneumoniae RfaHs. Results of biochemical and functional assays show that these proteins act similarly, with a notable difference between their interactions with the RNAP β subunit gate loop. We focused on high-affinity RfaH interactions with the RNAP β' subunit clamp helices as a shared target for inhibition. Among the top 10 leads identified by in silico docking using ZINC database, 3 ligands were able to inhibit E. coli RfaH recruitment in vitro. The most potent lead was active against both E. coli and K. pneumoniae RfaHs in vitro. Our results demonstrate the feasibility of identifying RfaH inhibitors using in silico docking and pave the way for rational design of antivirulence therapeutics against antibiotic-resistant pathogens.
Indexed as
Identifiers
What OpenQuestion holds
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.