The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species
In: Nature Communications, Jg. 15 (2024), Heft 1, S. 1-13
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Zugriff:
Abstract Triazoles, the most widely used class of antifungal drugs, inhibit the biosynthesis of ergosterol, a crucial component of the fungal plasma membrane. Inhibition of a separate ergosterol biosynthetic step, catalyzed by the sterol C-24 methyltransferase Erg6, reduces the virulence of pathogenic yeasts, but its effects on filamentous fungal pathogens like Aspergillus fumigatus remain unexplored. Here, we show that the lipid droplet-associated enzyme Erg6 is essential for the viability of A. fumigatus and other Aspergillus species, including A. lentulus, A. terreus, and A. nidulans. Downregulation of erg6 causes loss of sterol-rich membrane domains required for apical extension of hyphae, as well as altered sterol profiles consistent with the Erg6 enzyme functioning upstream of the triazole drug target, Cyp51A/Cyp51B. Unexpectedly, erg6-repressed strains display wild-type susceptibility against the ergosterol-active triazole and polyene antifungals. Finally, we show that erg6 repression results in significant reduction in mortality in a murine model of invasive aspergillosis. Taken together with recent studies, our work supports Erg6 as a potentially pan-fungal drug target.
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The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species
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Autor/in / Beteiligte Person: | Xie, Jinhong ; Rybak, Jeffrey M. ; Martin-Vicente, Adela ; Guruceaga, Xabier ; Thorn, Harrison I. ; Nywening, Ashley V. ; Ge, Wenbo ; Parker, Josie E. ; Kelly, Steven L. ; P. David Rogers ; Fortwendel, Jarrod R. |
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Zeitschrift: | Nature Communications, Jg. 15 (2024), Heft 1, S. 1-13 |
Veröffentlichung: | Nature Portfolio, 2024 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (print) |
DOI: | 10.1038/s41467-024-48767-3 |
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