Evidence map›Paper›PMID 25288678›Full record

ArticleThe Journal of antimicrobial chemotherapy2015

Expression of homologous RND efflux pump genes is dependent upon AcrB expression: implications for efflux and virulence inhibitor design.

Jessica M A Blair, Helen E Smith, Vito Ricci, Amelia J Lawler, Louisa J Thompson, Laura J V Piddock

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

53 citing papers in PubMed, 103 citations in OpenAlex.

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  14. Structural analysis of resistance-nodulation cell division transporters.Microbiology and molecular biology reviews : MMBR · 2024
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  16. Defense mechanisms ofFrontiers in antibiotics · 2024
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  19. Review
  20. Microbiology (Reading, England) · 2023
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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 1 institution in 1 country.

Jessica M A BlairAntimicrobials Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, and Institute of Microbiology and Infection, The University of Birmingham, Birmingham B15 2TT, UK.
Helen E SmithAntimicrobials Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, and Institute of Microbiology and Infection, The University of Birmingham, Birmingham B15 2TT, UK.
Vito RicciAntimicrobials Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, and Institute of Microbiology and Infection, The University of Birmingham, Birmingham B15 2TT, UK.
Amelia J LawlerAntimicrobials Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, and Institute of Microbiology and Infection, The University of Birmingham, Birmingham B15 2TT, UK.
Louisa J ThompsonAntimicrobials Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, and Institute of Microbiology and Infection, The University of Birmingham, Birmingham B15 2TT, UK.
Laura J V PiddockAntimicrobials Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, and Institute of Microbiology and Infection, The University of Birmingham, Birmingham B15 2TT, UK l.j.v.piddock@bham.ac.uk.
University of Birmingham · GB

Funding

Medical Research Council G0501415Medical Research Council GA2011-04R
6 · The paper itself

Abstract

objectivesEnterobacteriaceae have multiple efflux pumps that confer intrinsic resistance to antibiotics. AcrB mediates clinically relevant multidrug resistance and is required for virulence and biofilm formation, making it an attractive target for the design of inhibitors. The aim of this study was to assess the viability of single transporters as a target for efflux inhibition using Salmonella Typhimurium as the model pathogen.

methodsThe expression of resistance-nodulation-division (RND) efflux pump genes in response to the inactivation of single or multiple homologues was measured using real-time RT-PCR. Phenotypes of mutants were characterized by measuring antimicrobial susceptibility, dye accumulation and the ability to cause infection in vitro.

resultsThe expression of all RND efflux pump genes was increased when single or multiple acr genes were inactivated, suggesting a feedback mechanism that activates the transcription of homologous efflux pump genes. When two or three acr genes were inactivated, the mutants had further reduced efflux, altered susceptibility to antimicrobials (including increased susceptibility to some, but conversely and counterintuitively, decreased susceptibility to some others) and were more attenuated in the tissue culture model than mutants lacking single pumps were.

conclusionsThese data indicate that it is critical to understand which pumps an inhibitor is active against and the effect of this on the expression of homologous systems. For some antimicrobials, an inhibitor with activity against multiple pumps will have a greater impact on susceptibility, but an unintended consequence of this may be decreased susceptibility to other drugs, such as aminoglycosides.

Indexed as

Gene Expression Regulation, BacterialAnti-Bacterial AgentsDose-Response Relationship, DrugDrug Resistance, Multiple, BacterialGene Expression ProfilingGene SilencingGenotypeMembrane Transport ProteinsMicrobial Sensitivity TestsMultigene FamilyMutationSalmonella typhimuriumVirulenceAnti-Bacterial AgentsMembrane Transport ProteinsAcrBAcrDAcrFredundancy

Identifiers

PMID25288678
PMCPMC4291234
OpenAlexW2167048723

What OpenQuestion holds

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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.