Evidence map›Paper›PMID 34809453›Full record

ArticlemBio2021

A Histoplasma capsulatum Lipid Metabolic Map Identifies Antifungal Targets.

Daniel Zamith-Miranda, Heino M Heyman, Meagan C Burnet, Sneha P Couvillion, Xueyun Zheng, Nathalie Munoz, William C Nelson, Jennifer E Kyle, Erika M Zink, Karl K Weitz and 11 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Metabolomic signaling in sarcoidosis pathogenesis.Current opinion in immunology · 2026
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  12. Remodeling of theVaccines · 2020
    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

21 authors at 4 institutions in 1 country.

Daniel Zamith-Miranda *Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.ORCID 0000-0001-7532-2432
Heino M Heyman *Biological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Meagan C Burnet *Biological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Sneha P CouvillionBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Xueyun ZhengBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Nathalie MunozEnvironmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
William C NelsonBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.ORCID 0000-0002-1873-3929
Jennifer E KyleBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Erika M ZinkBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Karl K WeitzBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Kent J BloodsworthBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Geremy ClairBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.ORCID 0000-0003-0478-8520
Jeremy D ZuckerBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.ORCID 0000-0002-7276-9009
Jeremy R TeutonBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Samuel H PayneDepartment of Biology, Brigham Young University, Provo, Utah, USA.ORCID 0000-0002-8351-1994
Young-Mo KimBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.ORCID 0000-0002-8972-7593
Morayma Reyes GilHematology Laboratory, Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
Erin S BakerDepartment of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.
Erin L BredewegEnvironmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.
Joshua D NosanchukDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Ernesto S NakayasuBiological Sciences Division, Pacific Northwest National Laboratorygrid.451303.0, Richland, Washington, USA.ORCID 0000-0002-4056-2695
Pacific Northwest National Laboratory · USAlbert Einstein College of Medicine · USBrigham Young University · USNorth Carolina State University · US

Funding

Single cell, multi-parametric high throughput platform to classify endocrine disruptor potential of mixturesP42ES027704 · NIEHS · TEXAS A&M UNIVERSITY · PI Weihsueh A Chiu · 2017 to 2026
$21.2M
Antibody differentially alters Histoplasma extracellular vesiclesR21AI124797 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI NOSANCHUK, JOSHUA D · 2016 to 2017
$538k
NIAID NIH HHS R21 AI124797NIEHS NIH HHS P42 ES027704
6 · The paper itself

Abstract

Lipids play a fundamental role in fungal cell biology, being essential cell membrane components and major targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here, we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by incorporating proteomic and lipidomic analyses. We performed genetic complementation and overexpression of H. capsulatum genes in Saccharomyces cerevisiae to validate reactions identified in the map and to determine enzymes responsible for catalyzing orphan reactions. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We found that the sphingolipid biosynthesis inhibitor myriocin, the fatty acid desaturase inhibitor thiocarlide, and the fatty acid analog 10-thiastearic acid inhibit H. capsulatum growth in nanomolar to low-micromolar concentrations. These compounds also reduced the intracellular infection in an alveolar macrophage cell line. Overall, this lipid metabolic map revealed pathways that can be targeted for drug development.

Indexed as

Lipid MetabolismFatty AcidsFungal ProteinsHistoplasmaHistoplasmosisHumansLipidomicsProteomicsSphingolipidsFatty AcidsFungal ProteinsSphingolipidsdrug targetsHistoplasma capsulatumlipid metabolismlipidomicsmetabolic mapproteomics

Identifiers

PMID34809453
PMCPMC8609360
OpenAlexW3216121898

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.