Evidence map›Paper›PMID 18761689›Full record

ArticleMolecular microbiology2008

Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE Efflux pump system confer different levels of antimicrobial resistance and in vivo fitness.

Douglas M Warner, William M Shafer, Ann E Jerse

Open access · bronzeAbstract read
In one paragraph

Article in Molecular microbiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

130 citing papers in PubMed, 208 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Frontiers in microbiology · 2026
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Structural analysis of resistance-nodulation cell division transporters.Microbiology and molecular biology reviews : MMBR · 2024
    Review
  16. Review
  17. Article
  18. Rolling the evolutionary dice:Microbiology spectrum · 2024
    Article
  19. Article
  20. Article

70 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 2 institutions in 1 country.

Douglas M WarnerDepartment of Microbiology and Immunology, F. Edward Hèbert School of Medicine, Uniformed Services University, Bethesda, MD, USA.
William M Shafer
Ann E Jerse
In-Q-Tel · USVeterans Health Administration · US

Funding

Trichomonas Typing SystemU19AI031496 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SPARLING, PHILIP FREDERICK · 1995 to 2014
$24.9M
Gonococci: Genetics of Resistance to PMN ProteinsR37AI021150 · NIAID · EMORY UNIVERSITY · PI SHAFER, WILLIAM MAURICE · 2010 to 2019
$3.9M
GONOCOCCAL INFECTION AND GENE EXPRESSION IN FEMALE MICER01AI042053 · NIAID · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI JERSE, ANN E. · 1999 to 2014
$3.8M
Sexually Transmitted Infections &Antimicrobial PeptidesR01AI062755 · NIAID · EMORY UNIVERSITY · PI SHAFER, WILLIAM MAURICE · 2005 to 2009
$1.6M
NIAID NIH HHS R01 AI042053NIAID NIH HHS R01 AI062755NIAID NIH HHS R01-AI062755NIAID NIH HHS R01-AI42053NIAID NIH HHS R37 AI021150NIAID NIH HHS U19 AI031496NIAID NIH HHS U19 AI31496
6 · The paper itself

Abstract

The MtrC-MtrD-MtrE efflux pump system confers resistance to macrolide antibiotics and antimicrobial substances of the host innate defence. Clinical isolates with increased resistance to erythromycin and azithromycin frequently harbour mutations in the mtrR structural gene, which encodes a repressor of the mtrCDE operon, or the mtrR promoter region. The MtrC-MtrD-MtrE system is important for gonococcal survival in the murine genital tract, and derepression of the mtrCDE operon via deletion of mtrR confers increased fitness in vivo. Here we compared isogenic strains with naturally occurring mtrR locus mutations for differences in mtrCDE expression and pump-related phenotypes. Mutations upstream of mtrC, including those within the MtrR binding region and a novel mutation that increases mtrC RNA stability conferred the highest levels of derepression as measured by mtrCDE transcription and resistance to antibiotics, progesterone and antimicrobial peptides. In contrast, mutations within the mtrR coding sequence conferred low to intermediate levels of derepression. In vivo, the mtr mutants were more fit than the wild-type strain, the degree to which paralleled in vitro resistance gradients. These studies establish a hierarchy of mtrR locus mutations with regard to regulation of pump efflux, and suggest selection for more derepressed mutants may occur during mixed infections.

Indexed as

Drug Resistance, BacterialMutationAnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesAzithromycinBacterial Outer Membrane ProteinsBacterial ProteinsErythromycinFemaleGene Expression ProfilingGonorrheaLipoproteinsMembrane ProteinsMembrane Transport ProteinsMiceAnti-Bacterial AgentsAntimicrobial Cationic PeptidesAzithromycinBacterial Outer Membrane ProteinsBacterial ProteinsErythromycinLipoproteinsMembrane ProteinsMembrane Transport ProteinsMtrC protein, Neisseria gonorrhoeaeMtrD protein, Neisseria gonorrhoeaeMtrE protein, Neisseria gonorrhoeaemtrR protein, Neisseria gonorrhoeaeProgesteroneRepressor Proteins

Identifiers

PMID18761689
PMCPMC2602950
OpenAlexW1975300709

What OpenQuestion holds

Textmetadata
LicenceTDM
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.