Evidence map›Paper›PMID 19956582›Full record

ArticlePloS one2009

4-Bromophenacyl bromide specifically inhibits rhoptry secretion during Toxoplasma invasion.

Sandeep Ravindran, Melissa B Lodoen, Steven H L Verhelst, Matthew Bogyo, John C Boothroyd

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Ferlins and TgDOC2 inLife (Basel, Switzerland) · 2021
    Article
  3. Article
  4. A Window toPathogens (Basel, Switzerland) · 2018
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Evolution of apicomplexan secretory organelles.International journal for parasitology · 2012
    Review
  16. Article
  17. The secreted kinase ROP18 defends Toxoplasma's border.BioEssays : news and reviews in molecular, cellular and developmental biology · 2011
    Review
  18. 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 2 countries.

Sandeep RavindranDepartment of Microbiology and Immunology, Stanford University, Stanford, California, United States of America.
Melissa B Lodoen
Steven H L Verhelst
Matthew Bogyo
John C Boothroyd
Stanford University · USCenter for Integrated Protein Science Munich · DE

Funding

CORE 6 : PROJECT LEADERSHIP AND ADMINISTRATIONU54RR020843 · NCRR · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI SMITH, JEFFREY W · 2004 to 2009
$19.1M
Toxoplasma Rhoptry FunctionR01AI021423 · NIAID · STANFORD UNIVERSITY · PI BOOTHROYD, JOHN C · 1985 to 2018
$7.8M
Chemically Mapping Malarial Rupture ProteasesR01AI078947 · NIAID · STANFORD UNIVERSITY · PI BOGYO, MATTHEW · 2009 to 2013
$2.0M
ANTIGENS OF TOXOPLASMA GONDII AND THEIR GENESR37AI021423 · NIAID · STANFORD UNIVERSITY · PI BOOTHROYD, JOHN C · 1994 to 2003
$1.6M
NCRR NIH HHS RR020843NCRR NIH HHS U54 RR020843NIAID NIH HHS AI078947NIAID NIH HHS AI21423NIAID NIH HHS R01 AI021423NIAID NIH HHS R01 AI078947NIAID NIH HHS R37 AI021423
6 · The paper itself

Abstract

Toxoplasma gondii is a eukaryotic parasite of the phylum Apicomplexa that is able to infect a wide variety of host cells. During its active invasion process it secretes proteins from discrete secretory organelles: the micronemes, rhoptries and dense granules. Although a number of rhoptry proteins have been shown to be involved in important interactions with the host cell, very little is known about the mechanism of secretion of any Toxoplasma protein into the host cell. We used a chemical inhibitor of phospholipase A2s, 4-bromophenacyl bromide (4-BPB), to look at the role of such lipases in the secretion of Toxoplasma proteins. We found that 4-BPB was a potent inhibitor of rhoptry secretion in Toxoplasma invasion. This drug specifically blocked rhoptry secretion but not microneme secretion, thus effectively showing that the two processes can be de-coupled. It affected parasite motility and invasion, but not attachment or egress. Using propargyl- or azido-derivatives of the drug (so-called click chemistry derivatives) and a series of 4-BPB-resistant mutants, we found that the drug has a very large number of target proteins in the parasite that are involved in at least two key steps: invasion and intracellular growth. This potent compound, the modified "click-chemistry" forms of it, and the resistant mutants should serve as useful tools to further study the processes of Toxoplasma early invasion, in general, and rhoptry secretion, in particular.

Indexed as

AcetophenonesAnimalsCell AdhesionCell NucleusCytochalasin DHumansMembrane ProteinsMovementMutationParasitesProtozoan ProteinsToxoplasmaVacuoles4-bromophenacyl bromideAcetophenonesCytochalasin DMembrane ProteinsProtozoan ProteinsRON4 protein, Toxoplasma gondiiROP 1 protein, Toxoplasma gondii

Identifiers

PMID19956582
PMCPMC2780294
OpenAlexW2008554742

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.