Evidence map›Paper›PMID 26039584›Full record

ArticlePloS one2015

Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy.

Wooseong Kim, Annie L Conery, Rajmohan Rajamuthiah, Beth Burgwyn Fuchs, Frederick M Ausubel, Eleftherios Mylonakis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

49 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. How Bioactive Glass S53P4 Kills Bacteria.Journal of functional biomaterials · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024
    Review
  12. Article
  13. Article
  14. Loratadine Combats Methicillin-ResistantACS infectious diseases · 2024
    Article
  15. Review
  16. Article
  17. Article
  18. Bugs on Drugs: AMicroorganisms · 2022
    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

6 authors at 3 institutions in 1 country.

Wooseong KimDivision of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
Annie L ConeryDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Rajmohan RajamuthiahDivision of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America; Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Beth Burgwyn FuchsDivision of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America; Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Frederick M AusubelDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Eleftherios MylonakisDivision of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
Harvard University · USMassachusetts General Hospital · USRhode Island Hospital · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WHELAN, SEAN PJ · 2003 to 2013
$113.7M
Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Michael S Gilmore · 2009 to 2026
$39.4M
NIAID NIH HHS P01 AI083214NIAID NIH HHS U54 AI057159
6 · The paper itself

Abstract

Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA) persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7). In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

Indexed as

FluorescenceAnimalsAnti-Bacterial AgentsBiofilmsCaenorhabditis elegansDrug Evaluation, PreclinicalMethicillin-Resistant Staphylococcus aureusOrganic ChemicalsStaphylococcal InfectionsAnti-Bacterial AgentsOrganic ChemicalsSYTOX Green

Identifiers

PMID26039584
PMCPMC4454602
OpenAlexW2130825660

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.