Evidence map›Paper›PMID 29039719›Full record

ArticleMicrobial drug resistance (Larchmont, N.Y.)2018

Resistance in In Vitro Selected Tigecycline-Resistant Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Is Driven by Mutations in mepR and mepA Genes.

Andrei Nicoli Gebieluca Dabul, Juliana Sposto Avaca-Crusca, Daria Van Tyne, Michael S Gilmore, Ilana Lopes Baratella Cunha Camargo

Open access · bronzeAbstract read
In one paragraph

Article in Microbial drug resistance (Larchmont, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.4field-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

21 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Phenotypic and genetic stepwise changes inAntimicrobial agents and chemotherapy · 2025
    Article
  3. Article
  4. Staph wars: the antibiotic pipeline strikes back.Microbiology (Reading, England) · 2023
    Review
  5. Article
  6. Article
  7. Atopic dermatitis-derivedFrontiers in cellular and infection microbiology · 2023
    Article
  8. Genomic Insights of FirstInternational journal of molecular sciences · 2022
    Article
  9. Molecules (Basel, Switzerland) · 2022
    Article
  10. Review
  11. Frontiers in microbiology · 2022
    Article
  12. Article
  13. Article
  14. MarR family proteins are important regulators of clinically relevant antibiotic resistance.Protein science : a publication of the Protein Society · 2020
    Review
  15. Article
  16. Antimicrobial resistance in methicillin-resistantAntimicrobial agents and chemotherapy · 2019
    Review
  17. Antibiotic Resistance and the MRSA Problem.Microbiology spectrum · 2019
    Review
  18. Molecular basis for the emergence of a new hospital endemic tigecycline-resistant Enterococcus faecalis ST103 lineage.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2019
    Article
  19. Frontiers in microbiology · 2019
    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

5 authors at 4 institutions in 3 countries.

Andrei Nicoli Gebieluca Dabul1 Department of Physics and Interdisciplinary Science, São Carlos Institute of Physics, University of São Paulo , São Carlos, Brazil .
Juliana Sposto Avaca-Crusca1 Department of Physics and Interdisciplinary Science, São Carlos Institute of Physics, University of São Paulo , São Carlos, Brazil .
Daria Van Tyne2 Department of Ophthalmology, Harvard Medical School , Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
Michael S Gilmore2 Department of Ophthalmology, Harvard Medical School , Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
Ilana Lopes Baratella Cunha Camargo1 Department of Physics and Interdisciplinary Science, São Carlos Institute of Physics, University of São Paulo , São Carlos, Brazil .
Institute of Mathematics and Computer Science · MDHarvard University · USInstitute of Physics · PLMassachusetts Eye and Ear Infirmary · US

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Michael S Gilmore · 2009 to 2026
$39.4M
Bacterial Evasion of Innate Defenses at the Ocular SurfaceR00EY028222 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VAN TYNE, DARIA N · 2018 to 2020
$728k
Bacterial Evasion of Innate Defenses at the Ocular SurfaceK99EY028222 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI VAN TYNE, DARIA N · 2017 to 2017
$95k
NEI NIH HHS K99 EY028222NEI NIH HHS R00 EY028222NIAID NIH HHS P01 AI083214
6 · The paper itself

Abstract

A tigecycline-susceptible (TGC-S) Sequence Type (ST) 5 clinical methicillin-resistant Staphylococcus aureus (MRSA) strain was cultured in escalating levels of tigecycline, yielding mutants eightfold more resistant. Their genomes were sequenced to identify genetic alterations, resulting in resistance. Alterations in rpsJ, commonly related to tigecycline resistance, were also investigated. Tigecycline resistance was mediated by loss-of-function mutations in the transcriptional repressor mepR, resulting in derepression of the efflux pump mepA. Increased levels of resistance were obtained by successive mutations in mepA itself. No alterations in RpsJ were observed in selected strains, but we observed a K57M substitution, previously correlated with resistance, among TGC-S clinical strains. Thus, the pathway to tigecycline resistance in CC5 MRSA in vitro appears to be derepression of mep operon as the result of mepR loss-of-function mutation, followed by alterations in MepA efflux pump. This shows that other evolutionary pathways, besides mutation of rpsJ, are available for evolving tigecycline resistance in CC5 MRSA.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsGenome, BacterialMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsMinocyclineMutationStaphylococcal InfectionsTigecyclineAnti-Bacterial AgentsBacterial ProteinsMinocyclineTigecyclineMepAMepRMRSAtigecycline

Identifiers

PMID29039719
PMCPMC6037189
OpenAlexW2765795068

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.