Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Poster number: 28
Dolichol-dependent glycosylation; a prerequiste of
Candida albicans morphogenesis
Mateusz Juchimiuk 1 , Jacek Orłowski 1 , Joachim Ernst 2 Katarzyna
Gawarecka 1 , Ewa Kula Świeżewska 1 and Grażyna Palamarczyk 1
1 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawi skiego 5a,
02 106 Warsaw, Poland; 2 Department of Biology, Molecular Mycology, Heinrich-Heine-
Universitaet, Duesseldorf, Germany
An interesting feature of C. albicans biology is its ability to grow as unicellular
budding yeast, pseudohyphae, true hyphae and chlamydospore. The yeast to
hyphae transition is considered as a prerequisite of C. albicans virulence. On the
other hand, recent studies on the role of mannoproteins in C. albicans virulence
have demonstrated the importance of protein glycosylation for the fungal
pathogenesis. In the present work we characterized Candida albicans RER2 gene,
[cis-prenyltransferase (Rer2p) encoding]. Rer2p is the first enzyme of the
mevalonate pathway committed to the biosynthesis of dolichol, the isoprenoid lipid,
involved in protein glycosylation. A conditional mutant, expressing the C. albicans
ortholog of RER2 from the regulatable MET3 promoter, contained only 4 % of cisprenyltransferase
activity and markedly diminished amount of dolichols, when
cultivated in the repressive condition. Furthermore, at 28 o C the growth of the strain
was retarded and the strain was unable to grow at the restrictive temperature of 37
°C. Particularly, decreased dolichol level prevented morphological differentiation of
the strain leading to hyphae formation. Biochemical analysis confirmed
glycosylation disorder and compromised cell wall integrity. Our results suggest that
biosynthesis and level of dolichol and its ability to enter glycosylation pathway upon
phosphorylation, are essential not only for protein glycosylation and the cell wall
integrity but also for the growth and morphological differentiation of C. albicans
leading to virulence.
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