Evidence map›Paper›PMID 29251506›Full record

ArticleJournal of proteome research2018

Scanning Quadrupole Data-Independent Acquisition, Part B: Application to the Analysis of the Calcineurin-Interacting Proteins during Treatment of Aspergillus fumigatus with Azole and Echinocandin Antifungal Drugs.

Praveen R Juvvadi, M Arthur Moseley, Christopher J Hughes, Erik J Soderblom, Sarah Lennon, Simon R Perkins, J Will Thompson, Scott J Geromanos, Jason Wildgoose, Keith Richardson and 3 more

Abstract read
In one paragraph

Article in Journal of proteome research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

8 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Ultra-fast proteomics with Scanning SWATH.Nature biotechnology · 2021
    Article
  5. Review
  6. Frontiers in fungal biology · 2021
    Article
  7. Review
  8. 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

13 authors at 5 institutions in 2 countries.

Praveen R JuvvadiDivision of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center , Durham, North Carolina 27710, United States.
M Arthur MoseleyProteomics and Metabolomics Shared Resource Center for Genomic and Computational Biology, Duke University Medical Center , Durham, North Carolina 27710, United States.
Christopher J HughesWaters Corporation , Wilmslow SK9 4AX, United Kingdom.
Erik J SoderblomProteomics and Metabolomics Shared Resource Center for Genomic and Computational Biology, Duke University Medical Center , Durham, North Carolina 27710, United States.
Sarah LennonWaters Corporation , Wilmslow SK9 4AX, United Kingdom.
Simon R PerkinsInstitute of Integrative Biology, University of Liverpool , Liverpool L69 3BX, United Kingdom.
J Will ThompsonProteomics and Metabolomics Shared Resource Center for Genomic and Computational Biology, Duke University Medical Center , Durham, North Carolina 27710, United States.
Scott J GeromanosWaters Corporation , Milford, Massachusetts 01757, United States.
Jason WildgooseWaters Corporation , Wilmslow SK9 4AX, United Kingdom.
Keith RichardsonWaters Corporation , Wilmslow SK9 4AX, United Kingdom.
James I LangridgeWaters Corporation , Wilmslow SK9 4AX, United Kingdom.
Johannes P C VissersWaters Corporation , Wilmslow SK9 4AX, United Kingdom.ORCID 0000-0001-6283-8456
William J SteinbachDivision of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center , Durham, North Carolina 27710, United States.
Waters (United Kingdom) · GBDuke Medical Center · USDuke University · USUniversity of Liverpool · GBWaters (United States) · US

Funding

Defining the Aspergillus fumigatus Calcineurin-Dependent Regulatory Network through Whole Phosphoproteome AnalysisR21AI127551 · NIAID · DUKE UNIVERSITY · PI JUVVADI, PRAVEEN RAO, STEINBACH, WILLIAM J · 2017 to 2018
$437k
NIAID NIH HHS R21 AI127551
6 · The paper itself

Abstract

Calcineurin is a critical cell-signaling protein that orchestrates growth, stress response, virulence, and antifungal drug resistance in several fungal pathogens. Blocking calcineurin signaling increases the efficacy of several currently available antifungals and suppresses drug resistance. We demonstrate the application of a novel scanning quadrupole DIA method for the analysis of changes in the proteins coimmunoprecipitated with calcineurin during therapeutic antifungal drug treatments of the deadly human fungal pathogen Aspergillus fumigatus. Our experimental design afforded an assessment of the precision of the method as demonstrated by peptide- and protein-centric analysis from eight replicates of the study pool QC samples. Two distinct classes of clinically relevant antifungal drugs that are guideline recommended for the treatment of invasive "aspergillosis" caused by Aspergillus fumigatus, the azoles (voriconazole) and the echinocandins (caspofungin and micafungin), which specifically target the fungal plasma membrane and the fungal cell wall, respectively, were chosen to distinguish variations occurring in the proteins coimmunoprecipitated with calcineurin. Novel potential interactors were identified in response to the different drug treatments that are indicative of the possible role for calcineurin in regulating these effectors. Notably, treatment with voriconazole showed increased immunoprecipitation of key proteins involved in membrane ergosterol biosynthesis with calcineurin. In contrast, echinocandin (caspofungin or micafungin) treatments caused increased immunoprecipitation of proteins involved in cell-wall biosynthesis and septation. Furthermore, abundant coimmunoprecipitation of ribosomal proteins with calcineurin occurred exclusively in echinocandins treatment, indicating reprogramming of cellular growth mechanisms during different antifungal drug treatments. While variations in the observed calcineurin immunoprecipitated proteins may also be due to changes in their expression levels under different drug treatments, this study suggests an important role for calcineurin-dependent cellular mechanisms in response to antifungal treatment of A. fumigatus that warrants future studies.

Indexed as

Antifungal AgentsAspergillus fumigatusCalcineurinCaspofunginCell MembraneCell WallChromatography, LiquidEchinocandinsErgosterolFungal ProteinsGene ExpressionGene OntologyGenes, ReporterGreen Fluorescent ProteinsImmunoprecipitationLipopeptidesAntifungal AgentsCalcineurinCaspofunginEchinocandinsErgosterolFungal ProteinsGreen Fluorescent ProteinsLipopeptidesMicafunginRibosomal ProteinsVoriconazoleantifungal drug treatmentAspergillus fumigatuslabel-free quantitation

Identifiers

PMID29251506
PMCPMC5939564
OpenAlexW2781370959

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.