Evidence map›Paper›PMID 20804453›Full record

ArticleMolecular microbiology2010

Substrate path in the AcrB multidrug efflux pump of Escherichia coli.

Fasahath Husain, Hiroshi Nikaido

Abstract read
In one paragraph

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 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
–field-weighted citation impact
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

50 citing papers in PubMed.

  1. Article
  2. Regulation, structure, and activity of theAntimicrobial agents and chemotherapy · 2025
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Multidrug Resistance Pumps as a Keystone of Bacterial Resistance.Moscow University biological sciences bulletin · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Permeability barriers of Gram-negative pathogens.Annals of the New York Academy of Sciences · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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

2 authors.

Fasahath HusainDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.
Hiroshi Nikaido

Funding

BIOCHEMISTRY OF BACTERIAL CELL MEMBRANESR01AI009644 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI NIKAIDO, HIROSHI · 1985 to 2015
$9.7M
BIOCHEMISTRY OF BACTERIAL CELL MEMBRANESR37AI009644 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI NIKAIDO, HIROSHI · 1991 to 2000
$467k
NIAID NIH HHS AI-09644NIAID NIH HHS R01 AI009644NIAID NIH HHS R37 AI009644
6 · The paper itself

Abstract

A major tripartite multidrug efflux pump of Escherichia coli, AcrAB-TolC, confers resistance to a wide variety of compounds. The drug molecule is captured by AcrB probably from the periplasm or the periplasm/inner membrane interface, and is passed through AcrB and then TolC to the medium. Currently, there exist numerous crystallographic and mutation data concerning the regions of AcrB and its homologues that may interact with substrates. Starting with these data, we devised fluorescence assays in whole cells to determine the entire substrate path through AcrB. We tested 48 residues in AcrB along the predicted substrate path and 25 gave positive results, based on the covalent labelling of cysteine residues by a lipophilic dye-maleimide and the blocking of Nile red efflux by covalent labelling with bulky maleimide reagents. These residues are all located in the periplasmic domain, in regions we designate as the lower part of the large external cleft, the cleft itself, the crystallographically defined binding pocket, and the gate between the pocket and the funnel. Our observations suggest that the substrate is captured in the lower cleft region of AcrB, then transported through the binding pocket, the gate and finally to the AcrB funnel that connects AcrB to TolC.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsBacterial Outer Membrane ProteinsBinding SitesCysteineEscherichia coliEscherichia coli ProteinsFluorescent DyesMembrane Transport ProteinsMutagenesis, Site-DirectedProtein Structure, TertiaryStructure-Activity RelationshipSubstrate SpecificityAcrB protein, E coliATP-Binding Cassette, Sub-Family C ProteinsBacterial Outer Membrane ProteinsCysteineEscherichia coli ProteinsFluorescent DyesMembrane Transport ProteinstolC protein, E coli

Identifiers

PMID20804453
PMCPMC3008161

What OpenQuestion holds

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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.