Evidence map›Paper›PMID 18694955›Full record

ArticleAntimicrobial agents and chemotherapy2008

RamA confers multidrug resistance in Salmonella enterica via increased expression of acrB, which is inhibited by chlorpromazine.

Andrew M Bailey, Ian T Paulsen, Laura J V Piddock

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

71 citing papers in PubMed, 127 citations in OpenAlex.

  1. Article
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  9. Mapping direct and indirect MarA/SoxS/Rob/RamA regulons inMicrobiology (Reading, England) · 2023
    Article
  10. Review
  11. Review
  12. EnvR is a potent repressor of acrAB transcription in Salmonella.The Journal of antimicrobial chemotherapy · 2022
    Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

11 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Andrew M BaileyAntimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Ian T Paulsen
Laura J V Piddock
University of Birmingham · GB

Funding

Medical Research Council G0501415Medical Research Council GO501415Wellcome Trust
6 · The paper itself

Abstract

Salmonella enterica serovar Typhimurium SL1344, in which efflux pump genes (acrB, acrD, acrF, tolC) or regulatory genes thereof (marA, soxS, ramA) were inactivated, was grown in the presence of 240 antimicrobial and nonantimicrobial agents in the Biolog Phenotype MicroArray. Mutants lacking tolC, acrB, and ramA grew significantly worse than other mutants in the presence of 48 agents (some of which have not previously been identified as substrates of AcrAB-TolC) and particularly poorly in the presence of phenothiazines, which are human antipsychotics. MIC testing revealed that the phenothiazine chlorpromazine had antimicrobial activity and synergized with common antibiotics against different Salmonella serovars and SL1344. Chlorpromazine increased the intracellular accumulation of ethidium bromide, which was ablated in mutants lacking acrB, suggesting an interaction with AcrB. High-level but not low-level overexpression of ramA increased the expression of acrB; conferred resistance to chloramphenicol, tetracycline, nalidixic acid, and triclosan and organic solvent tolerance; and increased the amount of ethidium bromide accumulated. Chlorpromazine induced the modest overproduction of ramA but repressed acrB. These data suggest that phenothiazines are not efflux pump inhibitors but influence gene expression, including that of acrB, which confers the synergy with antimicrobials observed.

Indexed as

Anti-Bacterial AgentsAntipsychotic AgentsATP-Binding Cassette, Sub-Family C ProteinsBacterial ProteinsBase SequenceChlorpromazineDNA, BacterialDNA PrimersDrug Resistance, Multiple, BacterialDrug SynergismEthidiumGene ExpressionGenes, BacterialHumansMembrane Transport ProteinsMutationAcrB protein, Salmonella entericaAnti-Bacterial AgentsAntipsychotic AgentsATP-Binding Cassette, Sub-Family C ProteinsBacterial ProteinsChlorpromazineDNA, BacterialDNA PrimersEthidiumMembrane Transport ProteinsPhenothiazinesRamA protein, Salmonella typhimuriumTrans-Activators

Identifiers

PMID18694955
PMCPMC2565896
OpenAlexW2098164808

What OpenQuestion holds

Textmetadata
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.