Evidence map›Paper›PMID 26098625›Full record

ArticlePloS one2015

A High Throughput Screening Assay for Anti-Mycobacterial Small Molecules Based on Adenylate Kinase Release as a Reporter of Cell Lysis.

Lauren Forbes, Katherine Ebsworth-Mojica, Louis DiDone, Shao-Gang Li, Joel S Freundlich, Nancy Connell, Paul M Dunman, Damian J Krysan

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 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

10 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Discovery of a Natural Product That Binds to theMolecules (Basel, Switzerland) · 2020
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  7. Characterization of Two New Multidrug-Resistant Strains ofAntibiotics (Basel, Switzerland) · 2019
    Article
  8. Article
  9. Article
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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 2 institutions in 1 country.

Lauren ForbesDepartment of Microbiology/Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642, United States of America.
Katherine Ebsworth-MojicaDepartment of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642, United States of America.
Louis DiDoneDepartment of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642, United States of America.
Shao-Gang LiDepartment of Pharmacology, Rutgers University, Newark, New Jersey, 07103, United States of America.
Joel S FreundlichDepartment of Pharmacology, Rutgers University, Newark, New Jersey, 07103, United States of America; Department of Physiology, Rutgers University, Newark, New Jersey, 07103, United States of America; Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University, Newark, New Jersey, 07103, United States of America.
Nancy ConnellDepartment of Physiology, Rutgers University, Newark, New Jersey, 07103, United States of America; Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University, Newark, New Jersey, 07103, United States of America.
Paul M DunmanDepartment of Microbiology/Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642, United States of America.
Damian J KrysanDepartment of Microbiology/Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642, United States of America; Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, 14642, United States of America.
University of Rochester · USRutgers, The State University of New Jersey · US

Funding

Development of AK-based assays for antimicrobial screeningR01AI103507 · NIAID · UNIVERSITY OF ROCHESTER · PI DUNMAN, PAUL M. · 2013 to 2015
$1.1M
NIAID NIH HHS 5R01 AI103507NIAID NIH HHS R01 AI103507
6 · The paper itself

Abstract

Mycobacterium tuberculosis (Mtb) is well-established to be one of the most important bacterial pathogens for which new antimicrobial therapies are needed. Herein, we describe the development of a high throughput screening assay for the identification of molecules that are bactericidal against Mycobacteria. The assay utilizes the release of the intracellular enzyme adenylate kinase into the culture medium as a reporter of mycobacterial cell death. We demonstrate that the assay is selective for mycobactericidal molecules and detects anti-mycobacterial activity at concentrations below the minimum inhibitory concentration of many molecules. Thus, the AK assay is more sensitive than traditional growth assays. We have validated the AK assay in the HTS setting using the Mtb surrogate organism M. smegmatis and libraries of FDA approved drugs as well as a commercially available Diversity set. The screen of the FDA-approved library demonstrated that the AK assay is able to identify the vast majority of drugs with known mycobactericidal activity. Importantly, our screen of the Diversity set revealed that the increased sensitivity of the AK assay increases the ability of M. smegmatis-based screens to detect molecules with relatively poor activity against M. smegmatis but good to excellent activity against Mtb.

Indexed as

Adenylyl CyclasesAntitubercular AgentsDrug DiscoveryHigh-Throughput Screening AssaysMycobacteriumSmall Molecule LibrariesAdenylyl CyclasesAntitubercular AgentsSmall Molecule Libraries

Identifiers

PMID26098625
PMCPMC4476654
OpenAlexW2201570933

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.