Candida albicans cis-prenyltransferase Rer2 is required for protein glycosylation, cell wall integrity and hypha formation

•Two cis-prenyltransferases (Rer2 and Srt1) in Candida albicans were identified.•Rer2 is the main cis-prenyltransferase contributing >95% of enzymatic activity.•Hyphal morphogenesis is abolished if RER2 expression is reduced.•Decreased dolichol biosynthesis increases sensitivity to antifungals. c...

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Published in:Fungal genetics and biology 2014-08, Vol.69, p.1-12
Main Authors: Juchimiuk, Mateusz, Orłowski, Jacek, Gawarecka, Katarzyna, Świeżewska, Ewa, Ernst, Joachim F., Palamarczyk, Grażyna
Format: Article
Language:English
Subjects:
Candida albicans
Candida albicans - cytology
Candida albicans - enzymology
Candida albicans - growth & development
Candida albicans - physiology
Cell wall
Cell Wall - metabolism
cis-Prenyltransferase
Dolichol
Dolichol - analysis
Down-Regulation
Gene Expression
Gene Expression Profiling
Glycosylation
Hypha
Hyphae - growth & development
Protein glycosylation
Temperature
Transferases - genetics
Transferases - metabolism
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Summary:•Two cis-prenyltransferases (Rer2 and Srt1) in Candida albicans were identified.•Rer2 is the main cis-prenyltransferase contributing >95% of enzymatic activity.•Hyphal morphogenesis is abolished if RER2 expression is reduced.•Decreased dolichol biosynthesis increases sensitivity to antifungals. cis-Prenyltransferase is the first enzyme of the mevalonate pathway committed to the biosynthesis of dolichol in eukaryotes. The RER2 gene encoding cis-prenyltransferase (Rer2p) in the human fungal pathogen Candida albicans was characterized. In addition, the ORF19.5236 encoding the second cis-prenyltransferase, which putatively is responsible for the synthesis of longer polyisoprenoids chains, was identified. When cultivated under repressive conditions, the conditional mutant strain expressing the RER2 gene from the regulatable MET3 promoter contained only 4% of cis-prenyltransferase activity and markedly diminished amounts of dolichols, as compared to the wild-type strain. Moreover, transcriptomal analyses revealed changes in the expression of 300 genes, mainly involved in transport, response to stress, filamentous growth and organelle organization. Growth of the conditional strain was blocked completely at 37°C. The strain was hypersensitive to a wide range of inhibitors, which suggested glycosylation defects and compromised cell wall integrity. Moreover, the rer2 conditional mutant grown in the repressive conditions, unlike the same strain in the absence of repressor, failed to form hyphae. The results indicate that dolichols are essential not only for protein glycosylation and cell wall integrity but also for growth and development of C. albicans.
ISSN:1087-1845
1096-0937
DOI:10.1016/j.fgb.2014.05.004