Evidence map›Paper›PMID 30393188›Full record

ArticleInfection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases2019

Molecular basis for the emergence of a new hospital endemic tigecycline-resistant Enterococcus faecalis ST103 lineage.

Andrei Nicoli Gebieluca Dabul, Juliana Sposto Avaca-Crusca, Roberto Barranco Navais, Thaís Panhan Merlo, Daria Van Tyne, Michael S Gilmore, Ilana Lopes Baratella da Cunha Camargo

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Exploring Daptomycin Hypersensitivity inInternational journal of molecular sciences · 2025
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  2. Profiling Antibiotic Susceptibility among DistinctAntibiotics (Basel, Switzerland) · 2023
    Article
  3. Article
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  6. Mechanism of Eravacycline Resistance in ClinicalFrontiers in microbiology · 2020
    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

7 authors at 3 institutions in 3 countries.

Andrei Nicoli Gebieluca DabulSão Carlos Institute of Physics, University of São Paulo, PO Box 369, 135560-970 São Carlos, SP, Brazil.
Juliana Sposto Avaca-CruscaSão Carlos Institute of Physics, University of São Paulo, PO Box 369, 135560-970 São Carlos, SP, Brazil.
Roberto Barranco NavaisSão Carlos Institute of Physics, University of São Paulo, PO Box 369, 135560-970 São Carlos, SP, Brazil.
Thaís Panhan MerloSão Carlos Institute of Physics, University of São Paulo, PO Box 369, 135560-970 São Carlos, SP, Brazil.
Daria Van TyneDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, USA; Department of Microbiology and Immunobiology, Harvard Medical School, 25 Shattuck Street, Boston, USA.
Michael S GilmoreDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, USA; Department of Microbiology and Immunobiology, Harvard Medical School, 25 Shattuck Street, Boston, USA.
Ilana Lopes Baratella da Cunha CamargoSão Carlos Institute of Physics, University of São Paulo, PO Box 369, 135560-970 São Carlos, SP, Brazil. Electronic address: ilanacamargo@ifsc.usp.br.
Universidade de São Paulo · BRMassachusetts Eye and Ear Infirmary · USUniversidade Federal de São Carlos · BR

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Michael S Gilmore · 2009 to 2026
$39.4M
E. faecalis Pathogenicity IslandR01AI072360 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI GILMORE, MICHAEL S · 2007 to 2017
$3.8M
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 AI083214NIAID NIH HHS R01 AI072360
6 · The paper itself

Abstract

Enterococcus faecalis are a major cause of nosocomial infection worldwide, and the spread of vancomycin resistant strains (VRE) limits treatment options. Tigecycline-resistant VRE began to be isolated from inpatients at a Brazilian hospital within months following the addition of tigecycline to the hospital formulary. This was found to be the result of a spread of an ST103 E. faecalis clone. Our objective was to identify the basis for tigecycline resistance in this lineage. The genomes of two closely related tigecycline-susceptible (MIC = 0.06 mg/L), and three representative tigecycline-resistant (MIC = 1 mg/L) ST103 isolates were sequenced and compared. Further, efforts were undertaken to recapitulate the emergence of resistant strains in vitro. The specific mutations identified in clinical isolates in several cases were within the same genes identified in laboratory-evolved strains. The contribution of various polymorphisms to the resistance phenotype was assessed by trans-complementation of the wild type or mutant alleles, by testing for differences in mRNA abundance, and/or by examining the phenotype of transposon insertion mutants. Among tigecycline-resistant clinical isolates, five genes contained non-synonymous mutations, including two genes known to be related to enterococcal tigecycline resistance (tetM and rpsJ). Finally, within the in vitro-selected resistant variants, mutation in the gene for a MarR-family response regulator was associated with tigecycline resistance. This study shows that E. faecalis mutates to attain tigecycline resistance through the complex interplay of multiple mechanisms, along multiple evolutionary trajectories.

Indexed as

Drug Resistance, BacterialAnti-Bacterial AgentsCross InfectionDNA Transposable ElementsEnterococcus faecalisGene Expression Regulation, BacterialGenes, BacterialGenome, BacterialGenomicsGram-Positive Bacterial InfectionsHumansMicrobial Sensitivity TestsMutagenesis, InsertionalPhylogenyTigecyclineAnti-Bacterial AgentsDNA Transposable ElementsTigecyclinerpsJtetMTigecycline resistanceVancomycin-resistant enterococci

Identifiers

PMID30393188
PMCPMC6599719
OpenAlexW2898277364

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.