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FEBS Lett ; 525(1-3): 59-64, 2002 Aug 14.
Article in English | MEDLINE | ID: mdl-12163162

ABSTRACT

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.


Subject(s)
Antifungal Agents/pharmacology , Aspergillus fumigatus/metabolism , Aspergillus nidulans/metabolism , Enzyme Inhibitors/pharmacology , Glucosylceramides/biosynthesis , Glucosyltransferases/antagonists & inhibitors , Aspergillus fumigatus/chemistry , Aspergillus fumigatus/drug effects , Aspergillus nidulans/chemistry , Aspergillus nidulans/drug effects , Carbon Isotopes , Cell Cycle/drug effects , Cell Division/drug effects , Cerebrosides/analysis , Cerebrosides/biosynthesis , Fungal Proteins/antagonists & inhibitors , Fungal Proteins/metabolism , Galactosylceramides/analysis , Galactosylceramides/biosynthesis , Glucosylceramides/analysis , Glucosyltransferases/metabolism , Hyphae/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Pyrrolidines/pharmacology , Spores, Fungal/drug effects
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