Evidence map›Paper›PMID 22574132›Full record

ArticlePloS one2012

Identification and characterization of antifungal compounds using a Saccharomyces cerevisiae reporter bioassay.

Brad Tebbets, Douglas Stewart, Stephanie Lawry, Jeniel Nett, Andre Nantel, David Andes, Bruce S Klein

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 32 citations in OpenAlex.

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  7. The antifungal pipeline: a reality check.Nature reviews. Drug discovery · 2017
    Review
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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

7 authors at 2 institutions in 2 countries.

Brad TebbetsThe Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
Douglas Stewart
Stephanie Lawry
Jeniel Nett
Andre Nantel
David Andes
Bruce S Klein
University of Wisconsin–Madison · USBiotechnology Research Institute · CA

Funding

PROTECTIVE IMMUNE RESPONSES TO BLASTOMYCES DERMATITIDISR01AI040996 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BRUCE STEVEN, WUETHRICH, MARCEL · 1997 to 2023
$10.4M
Molecular Pathogenesis of BlastomycosisR37AI035681 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI BRUCE Steven KLEIN · 2004 to 2026
$6.9M
MOLECULAR PATHOGENESIS OF BLASTOMYCOSISR01AI035681 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BRUCE STEVEN · 1995 to 2019
$3.9M
Targeting hybrid histidine kinase for broad spectrum antifungal therapyRC1AI086025 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BRUCE STEVEN · 2009 to 2010
$994k
CIHR MOP-84341NIAID NIH HHS AI086025NIAID NIH HHS AI35681NIAID NIH HHS R01 AI035681NIAID NIH HHS R01 AI040996NIAID NIH HHS R37 AI035681NIAID NIH HHS RC1 AI086025
6 · The paper itself

Abstract

New antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. To identify drug leads, we screened small molecules using a Saccharomyces cerevisiae reporter bioassay in which S. cerevisiae heterologously expresses Hik1, a group III hybrid histidine kinase (HHK) from Magnaporthe grisea. Group III HHKs are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are absent in mammals, making them an attractive drug target. Our screen identified compounds 13 and 33, which showed robust activity against numerous fungal genera including Candida spp., Cryptococcus spp. and molds such as Aspergillus fumigatus and Rhizopus oryzae. Drug-resistant Candida albicans from patients were also highly susceptible to compounds 13 and 33. While the compounds do not act directly on HHKs, microarray analysis showed that compound 13 induced transcripts associated with oxidative stress, and compound 33, transcripts linked with heavy metal stress. Both compounds were highly active against C. albicans biofilm, in vitro and in vivo, and exerted synergy with fluconazole, which was inactive alone. Thus, we identified potent, broad-spectrum antifungal drug leads from a small molecule screen using a high-throughput, S. cerevisiae reporter bioassay.

Indexed as

Antifungal AgentsBiofilmsBiological AssayCandida albicansDNA DamageDNA RepairDrug Evaluation, PreclinicalDrug Resistance, FungalDrug SynergismFluconazoleGenes, ReporterHistidine KinaseMicrobial Sensitivity TestsOligonucleotide Array Sequence AnalysisProtein KinasesSaccharomyces cerevisiaeAntifungal AgentsFluconazoleHistidine KinaseProtein Kinases

Identifiers

PMID22574132
PMCPMC3344848
OpenAlexW2036809140

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.