ArticlePloS one2019
Chemogenomic profiling in yeast reveals antifungal mode-of-action of polyene macrolactam auroramycin.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.
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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.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters.Microbial cell factories · 2024Article
- Targeting trypanosomes: how chemogenomics and artificial intelligence can guide drug discovery.Biochemical Society transactions · 2023Review
- Plant as an Alternative Source of Antifungals againstPlants (Basel, Switzerland) · 2022Review
- Polyene Macrolactams from Marine and Terrestrial Sources: Structure, Production Strategies, Biosynthesis and Bioactivities.Marine drugs · 2022Review
- Biosynthetic engineering of the antifungal, anti-MRSA auroramycin.Microbial cell factories · 2020Article
- Antifungal and anti-mycotoxigenic activity of selected South African medicinal plants species.Heliyon · 2019Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we report antifungal activity of auroramycin against Candida albicans, Candida tropicalis, and Cryptococcus neoformans. Auroramycin, a potent antimicrobial doubly glycosylated 24-membered polyene macrolactam, was previously isolated and characterized, following CRISPR-Cas9 mediated activation of a silent polyketide synthase biosynthetic gene cluster in Streptomyces rosesporous NRRL 15998. Chemogenomic profiling of auroramycin in yeast has linked its antifungal bioactivity to vacuolar transport and membrane organization. This was verified by disruption of vacuolar structure and membrane integrity of yeast cells with auroramycin treatment. Addition of salt but not sorbitol to the medium rescued the growth of auroramycin-treated yeast cells suggesting that auroramycin causes ionic stress. Furthermore, auroramycin caused hyperpolarization of the yeast plasma membrane and displayed a synergistic interaction with cationic hygromycin. Our data strongly suggest that auroramycin inhibits yeast cells by causing leakage of cations from the cytoplasm. Thus, auroramycin's mode-of-action is distinct from known antifungal polyenes, reinforcing the importance of natural products in the discovery of new anti-infectives.
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Registered trials
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