ArticleMolecular microbiology2010
AcrA suppressor alterations reverse the drug hypersensitivity phenotype of a TolC mutant by inducing TolC aperture opening.
Article in Molecular microbiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 38 citations in OpenAlex.
- Structural shifts in TolC facilitate Efflux-Mediated β-lactam resistance.Communications biology · 2024Article
- Molecular Determinants for OMF Selectivity in Tripartite RND Multidrug Efflux Systems.Antibiotics (Basel, Switzerland) · 2022Article
- A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump.Antibiotics (Basel, Switzerland) · 2022Article
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.Chemical reviews · 2021Review
- Suppressor Mutations inJournal of bacteriology · 2019Article
- Muramyl Endopeptidase Spr Contributes to Intrinsic Vancomycin Resistance inFrontiers in microbiology · 2018Article
- Reviving Antibiotics: Efflux Pump Inhibitors That Interact with AcrA, a Membrane Fusion Protein of the AcrAB-TolC Multidrug Efflux Pump.ACS infectious diseases · 2017Article
- The Colicin E1 TolC Box: Identification of a Domain Required for Colicin E1 Cytotoxicity and TolC Binding.Journal of bacteriology · 2017Article
- Opening the Channel: the Two Functional Interfaces of Pseudomonas aeruginosa OpmH with the Triclosan Efflux Pump TriABC.Journal of bacteriology · 2016Article
- The Colicin E1 TolC-Binding Conformer: Pillar or Pore Function of TolC in Colicin Import?Biochemistry · 2016Article
- Tripartite assembly of RND multidrug efflux pumps.Nature communications · 2016Article
- Reversal of the Drug Binding Pocket Defects of the AcrB Multidrug Efflux Pump Protein of Escherichia coli.Journal of bacteriology · 2015Article
- Importance of Real-Time Assays To Distinguish Multidrug Efflux Pump-Inhibiting and Outer Membrane-Destabilizing Activities in Escherichia coli.Journal of bacteriology · 2015Article
- Catch me if you can: a biotinylated proteoliposome affinity assay for the investigation of assembly of the MexA-MexB-OprM efflux pump from Pseudomonas aeruginosa.Frontiers in microbiology · 2015Article
- Mechanism of coupling drug transport reactions located in two different membranes.Frontiers in microbiology · 2015Review
- Structural basis of RND-type multidrug exporters.Frontiers in microbiology · 2015Review
- Architecture and roles of periplasmic adaptor proteins in tripartite efflux assemblies.Frontiers in microbiology · 2015Review
- The ins and outs of RND efflux pumps in Escherichia coli.Frontiers in microbiology · 2015Review
- Genetic assessment of the role of AcrB β-hairpins in the assembly of the TolC-AcrAB multidrug efflux pump of Escherichia coli.Molecular microbiology · 2014Article
- 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
4 authors at 1 institution in 1 country.
Funding
Abstract
In Escherichia coli, the TolC-AcrAB complex forms a major antibiotic efflux system with broad substrate specificity. During the complex assembly, the periplasmic helices and bottom turns of TolC are thought to interact with a hairpin helix of AcrA and hairpin loops of AcrB respectively. In the present study we show that a four-residue substitution in TolC's turn 1, which connects outer helices 3 and 4 proximal to TolC's periplasmic aperture, confers antibiotic hypersensitivity, without affecting TolC-mediated phage or colicin infection. However, despite the null-like drug sensitivity phenotype, chemical cross-linking analysis revealed no apparent defects in the ability of the mutant TolC protein to physically interact with AcrA and AcrB. A role for TolC turn 1 residues in the functional assembly of the tripartite efflux pump complex was uncovered through isolating suppressor mutations of the mutant TolC protein that mapped within acrA and by utilizing a labile AcrA protein. The data showed that AcrA-mediated suppression of antibiotic sensitivity was achieved by dilating the TolC aperture/channel in an AcrB-dependent manner. The results underscore the importance of the periplasmic turn 1 of TolC in the functional assembly of the tripartite efflux complex and AcrA in transitioning TolC from its closed to open state.
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.