ArticlePLoS genetics2016
High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- A brief history of phosphatidylinositol transfer proteins: from the backwaters of cell biology to prime time in lipid signaling.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- A Cas3-base editing tool for targetable in vivo mutagenesis.Nature communications · 2023Article
- Beyond Ergosterol: Strategies for Combatting Antifungal Resistance inTetrahedron · 2023Article
- Regulation of phosphoinositide metabolism in Apicomplexan parasites.Frontiers in cell and developmental biology · 2023Review
- Small molecules for combating multidrug-resistant superbugActa pharmaceutica Sinica. B · 2022Review
- New strategies for combating fungal infections: Inhibiting inositol lipid signaling by targeting Sec14 phosphatidylinositol transfer proteins.Advances in biological regulation · 2022Review
- Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins.International journal of molecular sciences · 2021Review
- A marine microbiome antifungal targets urgent-threat drug-resistant fungi.Science (New York, N.Y.) · 2020Article
- Kendomycin Cytotoxicity against Bacterial, Fungal, and Mammalian Cells Is Due to Cation Chelation.Journal of natural products · 2020Article
- Lipid metabolism-related proteins of relevant evolutionary and lymphoid interest (PRELI) domain containing family proteins in cancer.American journal of translational research · 2020Review
- Modified carbazoles destabilize microtubules and kill glioblastoma multiform cells.European journal of medicinal chemistry · 2018Article
- Synthesis, Antifungal Activities and Molecular Docking Studies of Benzoxazole and Benzothiazole Derivatives.Molecules (Basel, Switzerland) · 2018Article
- Target Identification and Mechanism of Action of Picolinamide and Benzamide Chemotypes with Antifungal Properties.Cell chemical biology · 2018Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target. Consistent with this dual function, we demonstrate that NGx04 inhibits the growth of two clinical isolates of C. neoformans and that NGx04-related compounds have equal and even higher potency against C. neoformans. Furthermore NGx04 analogues showed fungicidal activity against a fluconazole resistant C. neoformans strain. In summary, we present genetic evidence that NGx04 inhibits fungal Sec14p and initial data supporting NGx04 as a novel antifungal starting point.
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