Evidence map›Paper›PMID 26747101›Full record

ArticleThe Journal of antimicrobial chemotherapy2016

Identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis.

Dafna Ben Yaakov, Anna Rivkin, Gabriel Mircus, Nathaniel Albert, Anna-Maria Dietl, Dimitry Kovalerchick, Shmuel Carmeli, Hubertus Haas, Dimitrios P Kontoyiannis, Nir Osherov

Abstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 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
–field-weighted citation impact
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.

  1. Review
  2. Frontiers in microbiology · 2024
    Review
  3. AlternativeFrontiers in cellular and infection microbiology · 2024
    Review
  4. Article
  5. Review
  6. Review
  7. In Vivo Efficacy of Voriconazole in aJournal of fungi (Basel, Switzerland) · 2021
    Article
  8. Article
  9. Review
  10. Microorganisms · 2020
    Review
  11. Bioactive Peptides Against Fungal Biofilms.Frontiers in microbiology · 2019
    Review
  12. The Use ofJournal of fungi (Basel, Switzerland) · 2018
    Review
  13. Therapy of Mucormycosis.Journal of fungi (Basel, Switzerland) · 2018
    Review
  14. Methodologies forMicrobial cell (Graz, Austria) · 2018
    Review
  15. Article
  16. 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

10 authors.

Dafna Ben YaakovDepartment of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Anna RivkinDepartment of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Gabriel MircusDepartment of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Nathaniel AlbertDepartment of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anna-Maria DietlBiocenter-Division of Molecular Biology, Medical University of Innsbruck, Innsbruck, Austria.
Dimitry KovalerchickRaymond and Beverly Sackler School of Chemistry and Faculty of Exact Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Shmuel CarmeliRaymond and Beverly Sackler School of Chemistry and Faculty of Exact Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Hubertus HaasBiocenter-Division of Molecular Biology, Medical University of Innsbruck, Innsbruck, Austria.
Dimitrios P KontoyiannisDepartment of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nir OsherovDepartment of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel nosherov@post.tau.ac.il.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Austrian Science Fund FWF P 25978Austrian Science Fund FWF W 1253
6 · The paper itself

Abstract

objectivesDuring recent decades, the number of invasive fungal infections among immunosuppressed patients has increased significantly, whereas the number of effective systemic antifungal drugs remains low and unsatisfactory. The aim of this study was to characterize a novel antifungal compound, CW-8/haemofungin, which we previously identified in a screen for compounds affecting fungal cell wall integrity.

methodsThe in vitro characteristics of haemofungin were investigated by MIC evaluation against a panel of pathogenic and non-pathogenic fungi, bacteria and mammalian cells in culture. Haemofungin mode-of-action studies were performed by screening an Aspergillus nidulans overexpression genomic library for resistance-conferring plasmids and biochemical validation of the target. In vivo efficacy was tested in the Galleria mellonella and Drosophila melanogaster insect models of infection.

resultsWe demonstrate that haemofungin causes swelling and lysis of growing fungal cells. It inhibits the growth of pathogenic Aspergillus, Candida, Fusarium and Rhizopus isolates at micromolar concentrations, while only weakly affecting the growth of mammalian cell lines. Genetic and biochemical analyses in A. nidulans and Aspergillus fumigatus indicate that haemofungin primarily inhibits ferrochelatase (HemH), the last enzyme in the haem biosynthetic pathway. Haemofungin was non-toxic and significantly reduced mortality rates of G. mellonella and D. melanogaster infected with A. fumigatus and Rhizopus oryzae, respectively.

conclusionsFurther development and in vivo validation of haemofungin is warranted.

Indexed as

AnimalsAntifungal AgentsAspergillus nidulansBacteriaCell LineDrug Resistance, FungalDrug SynergismFerrochelataseFungiHemeHeterocyclic Compounds, 4 or More RingsHumansInsectaMicrobial Sensitivity TestsMycosesProtoporphyrinsAntifungal AgentsFerrochelatasehaemofunginHemeHeterocyclic Compounds, 4 or More Ringsprotoporphyrin IXProtoporphyrins

Identifiers

PMID26747101
PMCPMC5757792

What OpenQuestion holds

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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.