Evidence map›Paper›PMID 27594549›Full record

ArticleBioorganic & medicinal chemistry2016

Accelerating the discovery of antibacterial compounds using pathway-directed whole cell screening.

Leigh M Matano, Heidi G Morris, B McKay Wood, Timothy C Meredith, Suzanne Walker

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry, 2016. 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
2.1field-weighted citation impact, top 13% 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, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Oligopeptide Sortase Inhibitor ModulatesAntibiotics (Basel, Switzerland) · 2022
    Article
  10. Review
  11. Rapid Inhibitor Discovery by Exploiting Synthetic Lethality.Journal of the American Chemical Society · 2022
    Article
  12. Article
  13. Review
  14. 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

5 authors at 2 institutions in 1 country.

Leigh M MatanoDepartment of Microbiology and Immunobiology, 4 Blackfan Circle, Boston, MA 02115, USA.
Heidi G MorrisDepartment of Microbiology and Immunobiology, 4 Blackfan Circle, Boston, MA 02115, USA.
B McKay WoodDepartment of Microbiology and Immunobiology, 4 Blackfan Circle, Boston, MA 02115, USA.
Timothy C MeredithDepartment of Biochemistry and Molecular Biology, 206 South Frear Laboratory, University Park, PA 16802, USA. Electronic address: txm50@psu.edu.
Suzanne WalkerDepartment of Microbiology and Immunobiology, 4 Blackfan Circle, Boston, MA 02115, USA. Electronic address: Suzanne_walker@hms.harvard.edu.
Circle (United States) · USPark University · US

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Johan Paulsson · 2009 to 2026
$39.4M
Targeting bacterial cell wall biogenesis for the development of novel antimicrobU19AI109764 · NIAID · HARVARD MEDICAL SCHOOL · PI BERNHARDT, THOMAS G · 2014 to 2018
$25.2M
NIAID NIH HHS P01 AI083214NIAID NIH HHS U19 AI109764
6 · The paper itself

Abstract

Since the introduction of penicillin into the clinic in 1942, antibiotics have saved the lives of millions of people around the world. While penicillin and other traditional broad spectrum antibiotics were effective as monotherapies, the inexorable spread of antibiotic resistance has made alternative therapeutic approaches necessary. Compound combinations are increasingly seen as attractive options. Such combinations may include: lethal compounds; synthetically lethal compounds; or administering a lethal compound with a nonlethal compound that targets a virulence factor or a resistance factor. Regardless of the therapeutic strategy, high throughput screening is a key approach to discover potential leads. Unfortunately, the discovery of biologically active compounds that inhibit a desired pathway can be a very slow process, and an inordinate amount of time is often spent following up on compounds that do not have the desired biological activity. Here we describe a pathway-directed high throughput screening paradigm that combines the advantages of target-based and whole cell screens while minimizing the disadvantages. By exploiting this paradigm, it is possible to rapidly identify biologically active compounds that inhibit a pathway of interest. We describe some previous successful applications of this paradigm and report the discovery of a new class of d-alanylation inhibitors that may be useful as components of compound combinations to treat methicillin-resistant Staphylococcus aureus (MRSA).

Indexed as

Drug DiscoveryHigh-Throughput Screening AssaysAnti-Bacterial AgentsMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsMolecular StructureStructure-Activity RelationshipAnti-Bacterial Agentsd-AlanylationHigh throughput screenPathway-directed drug discoveryTeichoic acidTransposon sequencing

Identifiers

PMID27594549
PMCPMC5180449
OpenAlexW2513701128

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.