Evidence map›Paper›PMID 27381387›Full record

ArticleAntimicrobial agents and chemotherapy2016

The Heterodimeric ABC Transporter EfrCD Mediates Multidrug Efflux in Enterococcus faecalis.

Lea M Hürlimann, Valentina Corradi, Michael Hohl, Guido V Bloemberg, D Peter Tieleman, Markus A Seeger

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 53 citations in OpenAlex.

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  12. Biomolecules · 2022
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  13. The repertoire of ABC proteins inComputational and structural biotechnology journal · 2021
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  18. Cloning and Functional Characterization of PutativeJournal of microbiology and biotechnology · 2020
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  20. Frontiers in microbiology · 2020
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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

6 authors at 2 institutions in 2 countries.

Lea M HürlimannInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
Valentina CorradiCentre for Molecular Simulation and Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
Michael HohlInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
Guido V BloembergInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
D Peter TielemanCentre for Molecular Simulation and Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
Markus A SeegerInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland m.seeger@imm.uzh.ch.
University of Zurich · CHUniversity of Calgary · CA

Funding

CIHR MOP-62690
6 · The paper itself

Abstract

Nosocomial infections with Enterococcus faecalis are an emerging health problem. However, drug efflux pumps contributing to intrinsic drug resistance are poorly studied in this Gram-positive pathogen. In this study, we functionally investigated seven heterodimeric ABC transporters of E. faecalis that are annotated as drug efflux pumps. Deletion of ef0789-ef0790 on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342, and the corresponding transporter was named EfrCD. Unexpectedly, the previously described heterodimeric multidrug ABC transporter EfrAB contributes marginally to drug efflux in the endogenous context of E. faecalis In contrast, heterologous expression in Lactococcus lactis revealed that EfrAB, EfrCD, and the product of ef2226-ef2227 (EfrEF) mediate the efflux of fluorescent substrates and confer resistance to multiple dyes and drugs, including fluoroquinolones. Four of seven transporters failed to exhibit drug efflux activity for the set of drugs and dyes tested, even upon overexpression in L. lactis Since all seven transporters were purified as heterodimers after overexpression in L. lactis, a lack of drug efflux activity is not attributed to poor expression or protein aggregation. Reconstitution of the purified multidrug transporters EfrAB, EfrCD, and EfrEF in proteoliposomes revealed functional coupling between ATP hydrolysis and drug binding. Our analysis creates an experimental basis for the accurate prediction of drug efflux transporters and indicates that many annotated multidrug efflux pumps might be incapable of drug transport and thus might fulfill other physiological functions in the cell.

Indexed as

Adenosine TriphosphateAmino Acid SequenceAnti-Bacterial AgentsATP-Binding Cassette TransportersBacterial ProteinsBase SequenceBenzimidazolesBiological TransportChromosomes, BacterialDaunorubicinDoxorubicinEnterococcus faecalisEthidiumFluoroquinolonesGene ExpressionGenetic LociAdenosine TriphosphateAnti-Bacterial AgentsATP-Binding Cassette TransportersBacterial ProteinsBenzimidazolesbisbenzimide ethoxide trihydrochlorideDaunorubicinDoxorubicinEthidiumFluoroquinolonesProteolipidsproteoliposomesRecombinant Proteins

Identifiers

PMID27381387
PMCPMC4997860
OpenAlexW2468854408

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.