Author Correction: Jawsamycin exhibits in vivo antifungal properties by inhibiting Spt14/Gpi3-mediated biosynthesis of glycosylphosphatidylinositol
| العنوان: | Author Correction: Jawsamycin exhibits in vivo antifungal properties by inhibiting Spt14/Gpi3-mediated biosynthesis of glycosylphosphatidylinositol |
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| المؤلفون: | Jianshi Tao, Frank Petersen, Eric Weber, David Estoppey, Vivian Prindle, Sven Schuierer, Christian Studer, Dominik Pistorius, Jürg Hunziker, Etienne Richard, Manuel Mihalic, Klaus Memmert, Ralph Riedl, Silvio Roggo, Ashraf S. Ibrahim, Dominic Hoepfner, Yue Fu, Florian Fuchs, Thomas Aust, Frederic Grandjean |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-1 (2020) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Antifungal, Saccharomyces cerevisiae Proteins, Glycosylphosphatidylinositols, medicine.drug_class, Glycosylphosphatidylinositol, Science, General Physics and Astronomy, Saccharomyces cerevisiae, Article, General Biochemistry, Genetics and Molecular Biology, Inhibitory Concentration 50, Mice, chemistry.chemical_compound, Biosynthesis, Genes, Reporter, In vivo, Target identification, medicine, Animals, Humans, lcsh:Science, Author Correction, Lung, Antifungal agents, Cell Proliferation, Mice, Inbred ICR, Multidisciplinary, Chemistry, Fungi, Glycosyltransferases, Hep G2 Cells, General Chemistry, Hydrogen-Ion Concentration, HCT116 Cells, Disease Models, Animal, Biochemistry, Multigene Family, Polyketides, Fermentation, Mucorales, lcsh:Q, Pathogens, K562 Cells, Rhizopus |
| الوصف: | Biosynthesis of glycosylphosphatidylinositol (GPI) is required for anchoring proteins to the plasma membrane, and is essential for the integrity of the fungal cell wall. Here, we use a reporter gene-based screen in Saccharomyces cerevisiae for the discovery of antifungal inhibitors of GPI-anchoring of proteins, and identify the oligocyclopropyl-containing natural product jawsamycin (FR-900848) as a potent hit. The compound targets the catalytic subunit Spt14 (also referred to as Gpi3) of the fungal UDP-glycosyltransferase, the first step in GPI biosynthesis, with good selectivity over the human functional homolog PIG-A. Jawsamycin displays antifungal activity in vitro against several pathogenic fungi including Mucorales, and in vivo in a mouse model of invasive pulmonary mucormycosis due to Rhyzopus delemar infection. Our results provide a starting point for the development of Spt14 inhibitors for treatment of invasive fungal infections. Biosynthesis of glycosylphosphatidylinositol (GPI) is essential for the integrity of the fungal cell wall. Here, the authors show that the natural product jawsamycin inhibits GPI biosynthesis by targeting a subunit of the fungal UDP-glycosyltransferase, and displays pronounced activity against pathogenic fungi of the order Mucorales. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::044c1d078bd50f0a4ee8f0a580be2d6d https://doaj.org/article/d2b7f75c0b374df0a687c5171d690a4d |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....044c1d078bd50f0a4ee8f0a580be2d6d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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