Evidence map›Paper›PMID 27631336›Full record

ArticlePLoS biology2016

Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy.

Dilay Hazal Ayhan, Yusuf Talha Tamer, Mohammed Akbar, Stacey M Bailey, Michael Wong, Seth M Daly, David E Greenberg, Erdal Toprak

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
8.1field-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

44 citing papers in PubMed, 86 citations in OpenAlex.

  1. Oligonucleotide genetics forbioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Article
  4. Efflux-Mediated Resistance inAntibiotics (Basel, Switzerland) · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Comparison of Phenotype and Genotype Virulence and Antimicrobial Factors ofInternational journal of molecular sciences · 2023
    Article
  15. Article
  16. Article
  17. Review
  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

8 authors at 5 institutions in 1 country.

Dilay Hazal AyhanGreen Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.ORCID 0000-0002-0497-3294
Yusuf Talha TamerGreen Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.ORCID 0000-0002-5901-842X
Mohammed AkbarGreen Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.ORCID 0000-0003-1832-2043
Stacey M BaileySarepta Therapeutics, Cambridge, Massachusetts, United States of America.ORCID 0000-0002-8356-8384
Michael WongSarepta Therapeutics, Cambridge, Massachusetts, United States of America.
Seth M DalyDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
David E GreenbergDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Erdal ToprakGreen Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Center for Systems Biology · USThe University of Texas Southwestern Medical Center · USHarvard University · USSarepta Therapeutics (United States) · USUniversity of Massachusetts Amherst · US

Funding

Novel gene-silencing therapeutics for multidrug-resistant gram-negative pathogensR33AI098724 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GREENBERG, DAVID ELIHU · 2014 to 2016
$1.1M
NIAID NIH HHS R33 AI098724
6 · The paper itself

Abstract

The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene's sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities.

Indexed as

Anti-Bacterial AgentsBase SequenceCarrier ProteinsCell LineDrug Resistance, BacterialEscherichia coli ProteinsGene Knockdown TechniquesGenes, BacterialHumansMicrobial Sensitivity TestsOligodeoxyribonucleotides, AntisensePenicillanic AcidPiperacillinSulfamethoxazoleTazobactamTrimethoprimAcrAB-TolC protein, E coliAnti-Bacterial AgentsCarrier ProteinsEscherichia coli ProteinsOligodeoxyribonucleotides, AntisensePenicillanic AcidPiperacillinSulfamethoxazoleTazobactamTrimethoprim

Identifiers

PMID27631336
PMCPMC5025249
OpenAlexW2519994145

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.