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Disruption of the glucosylceramide biosynthetic pathway in Aspergillus nidulans and Aspergillus fumigatus by inhibitors of UDP‐Glc:ceramide glucosyltransferase strongly affects spore germination, cell cycle, and hyphal growth
Author(s) -
Levery Steven B,
Momany Michelle,
Lindsey Rebecca,
Toledo Marcos S,
Shayman James A,
Fuller Matthew,
Brooks Kelly,
Doong Ron Lou,
Straus Anita H,
Takahashi Helio K
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03067-3
Subject(s) - aspergillus nidulans , aspergillus fumigatus , ceramide , hypha , biochemistry , spore germination , biology , microbiology and biotechnology , chemistry , spore , apoptosis , gene , mutant
The opportunistic mycopathogen Aspergillus fumigatus expresses both glucosylceramide and galactosylceramide (GlcCer and GalCer), but their functional significance in Aspergillus species is unknown. We here identified and characterized a GlcCer from Aspergillus nidulans , a non‐pathogenic model fungus. Involvement of GlcCer in fungal development was tested on both species using a family of compounds known to inhibit GlcCer synthase in mammals. Two analogs, D ‐ threo ‐1‐phenyl‐2‐palmitoyl‐3‐pyrrolidinopropanol (P4) and D ‐ threo ‐3′,4′‐ethylenedioxy‐P4, strongly inhibited germination and hyphal growth. Neutral lipids from A. fumigatus cultured in the presence of these inhibitors displayed a significantly reduced GlcCer/GalCer ratio. These results suggest that synthesis of GlcCer is essential for normal development of A. fumigatus and A. nidulans .