Evidence map›Paper›PMID 25582336›Full record

ArticleMolecular microbiology2015

Transcriptome analysis of cyclic AMP-dependent protein kinase A-regulated genes reveals the production of the novel natural compound fumipyrrole by Aspergillus fumigatus.

Juliane Macheleidt, Kirstin Scherlach, Toni Neuwirth, Wolfgang Schmidt-Heck, Maria Straßburger, Joseph Spraker, Joshua A Baccile, Frank C Schroeder, Nancy P Keller, Christian Hertweck and 2 more

Open access · greenAbstract read
In one paragraph

Article in Molecular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. A Timeline of Biosynthetic Gene Cluster Discovery inJournal of fungi (Basel, Switzerland) · 2024
    Article
  4. The Transcriptome Response to Azole Compounds inJournal of fungi (Basel, Switzerland) · 2023
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Exposure ofJournal of fungi (Basel, Switzerland) · 2020
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Animal Models of Aspergillosis.Comparative medicine · 2018
    Review
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

12 authors at 4 institutions in 2 countries.

Juliane MacheleidtMolecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), 07745, Jena, Germany; Institute for Microbiology, Friedrich Schiller University, 07745, Jena, Germany.
Kirstin Scherlach
Toni Neuwirth
Wolfgang Schmidt-Heck
Maria Straßburger
Joseph Spraker
Joshua A Baccile
Frank C Schroeder
Nancy P Keller
Christian Hertweck
Thorsten Heinekamp
Axel A Brakhage
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) · DEFriedrich Schiller University Jena · DECornell University · USUniversity of Wisconsin System · US

Funding

CHEMISTRY OF BIOLOGICAL SYSTEMST32GM008500 · NIGMS · CORNELL UNIVERSITY ITHACA · PI LIN, HENING · 1996 to 2020
$5.4M
Comprehensive analysis of NRPS-derived metabolomes of three Aspergillus speciesR01GM112739 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI KELLER, NANCY P · 2015 to 2023
$2.8M
NIGMS NIH HHS R01 GM112739NIGMS NIH HHS T32 GM008500
6 · The paper itself

Abstract

Aspergillus fumigatus is an opportunistic human pathogenic fungus causing life-threatening infections in immunocompromised patients. Adaptation to different habitats and also virulence of the fungus depends on signal perception and transduction by modules such as the cyclic AMP-dependent protein kinase A (PKA) pathway. Here, by transcriptome analysis, 632 differentially regulated genes of this important signaling cascade were identified, including 23 putative transcriptional regulators. The highest upregulated transcription factor gene was located in a previously unknown secondary metabolite gene cluster, which we named fmp, encoding an incomplete non-ribosomal peptide synthetase, FmpE. Overexpression of the regulatory gene fmpR using the Tet(On) system led to the specific expression of the other six genes of the fmp cluster. Metabolic profiling of wild type and fmpR overexpressing strain by HPLC-DAD and HPLC-HRESI-MS and structure elucidation by NMR led to identification of 5-benzyl-1H-pyrrole-2-carboxylic acid, which we named fumipyrrole. Fumipyrrole was not described as natural product yet. Chemical synthesis of fumipyrrole confirmed its structure. Interestingly, deletion of fmpR or fmpE led to reduced growth and sporulation of the mutant strains. Although fmp cluster genes were transcribed in infected mouse lungs, deletion of fmpR resulted in wild-type virulence in a murine infection model.

Indexed as

Gene Expression ProfilingGene Expression Regulation, FungalAnimalsAspergillus fumigatusCyclic AMPCyclic AMP-Dependent Protein KinasesDisease Models, AnimalFungal ProteinsLungMiceMultigene FamilyPeptide SynthasesProlinePulmonary AspergillosisSignal Transduction2-pyrrolecarboxylic acidCyclic AMPCyclic AMP-Dependent Protein KinasesFungal ProteinsPeptide SynthasesProline

Identifiers

PMID25582336
PMCPMC4425693
OpenAlexW2120114420

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Registered trials

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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.