Evidence map›Paper›PMID 27183222›Full record

ArticlePloS one2016

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A.

Chelsi D Cassilly, Marcus M Maddox, Philip T Cherian, John J Bowling, Mark T Hamann, Richard E Lee, Todd B Reynolds

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Lipid Transport byInfection and immunity · 2022
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Plasma Membrane MCC/Eisosome Domains Promote Stress Resistance in Fungi.Microbiology and molecular biology reviews : MMBR · 2020
    Review
  11. Article
  12. Article
  13. Article
  14. Lipid Biosynthesis as an Antifungal Target.Journal of fungi (Basel, Switzerland) · 2018
    Review
  15. Review
  16. 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 1 country.

Chelsi D CassillyDepartment of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.
Marcus M MaddoxDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States of America.
Philip T CherianDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States of America.
John J BowlingDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States of America.
Mark T HamannDepartment of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Richard E LeeDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States of America.
Todd B ReynoldsDepartment of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.
St. Jude Children's Research Hospital · USUniversity of Tennessee at Knoxville · USMedical University of South Carolina · US

Funding

Screen for phosphatidylserine synthase inhibitors: antifungals & lipid probesR01AI105690 · NIAID · UNIVERSITY OF TENNESSEE KNOXVILLE · PI REYNOLDS, TODD B · 2013 to 2015
$1.2M
NIAID NIH HHS R01 AI105690
6 · The paper itself

Abstract

In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS) synthase (Cho1p) was developed based on antagonism of the toxin papuamide A (Pap-A). Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ) do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A) as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A), but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins.

Indexed as

Antifungal AgentsCandida albicansCDPdiacylglycerol-Serine O-PhosphatidyltransferaseDepsipeptidesDrug AntagonismDrug DiscoveryDrug Resistance, FungalHigh-Throughput Screening AssaysMicrobial Sensitivity TestsMolecular StructurePiperidonesSpiro CompoundsAntifungal AgentsCDPdiacylglycerol-Serine O-PhosphatidyltransferaseDepsipeptidespapuamide APiperidonesSB 22489GSpiro Compoundstheopapuamide

Identifiers

PMID27183222
PMCPMC4868317
OpenAlexW2395240076

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.