Evidence map›Paper›PMID 29551265›Full record

ArticleCell2018

Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance.

Anna Rubio-Cosials, Eike C Schulz, Lotte Lambertsen, Georgy Smyshlyaev, Carlos Rojas-Cordova, Kristoffer Forslund, Ezgi Karaca, Aleksandra Bebel, Peer Bork, Orsolya Barabas

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
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  8. Transposition mechanism of ISAntimicrobial agents and chemotherapy · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

Anna Rubio-CosialsStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Eike C SchulzStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Hamburg Outstation, European Molecular Biology Laboratory, 22603 Hamburg, Germany.
Lotte LambertsenStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Georgy SmyshlyaevStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton CB10 1SD, UK.
Carlos Rojas-CordovaStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Kristoffer ForslundStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Ezgi KaracaStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Izmir Biomedicine and Genome Center (IBG), 35340 Izmir, Turkey.
Aleksandra BebelStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Peer BorkStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany; Molecular Medicine Partnership Unit, 69120 Heidelberg, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Orsolya BarabasStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany. Electronic address: barabas@embl.de.
European Molecular Biology Laboratory · DEEuropean Bioinformatics Institute · GBEuropean Molecular Biology Laboratory · DEIzmir University · TRMax Delbrück Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes.

Indexed as

Amino Acid SequenceBase SequenceBinding SitesCatalytic DomainCrystallography, X-RayDNA, BacterialDNA CleavageDNA Transposable ElementsDrug Resistance, BacterialEnterococcus faecalisModels, MolecularMolecular Dynamics SimulationMutagenesis, Site-DirectedNucleic Acid ConformationProtein BindingProtein Structure, TertiaryDNA, BacterialDNA Transposable ElementsRecombinant ProteinsTransposasesantibiotic resistanceconjugative transpositioncrystallographyDNA complexgene transfermultidrug-resistant bacteriaTn1549 transposonTn916-like transposon familytyrosine recombinasevancomycin

Identifiers

PMID29551265
PMCPMC5871717
OpenAlexW2793802940

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.