The Essential Rot1 Protein Links Glycosylation, Cell Wall Integrity, and Pathogenic Development in Candida albicans

Abstract

The Rot1 protein is a chaperone involved in glycosylation, dolichol phosphorylation, cell wall synthesis, and protein folding in the yeast Saccharomyces cerevisiae. Available information on cell wall defects in the S. cerevisiae rot1-1 mutant and the association of Rot1 with protein glycosylation suggest that in the case of Candida albicans, Rot1 may be involved in pathogenesis, since both cell wall synthesis and protein glycosylation are closely related to the formation of pathogenic structures in C. albicans. As Rot1 has not been found in humans, it seems particularly attractive for study in the context of C. albicans pathogenicity. This protein takes on additional significance because deletion of the gene that encodes Rot1 is lethal for yeast. In this study, we cloned and analyzed the function of the candidate protein CaRot1 from C. albicans in the S. cerevisiae rot1∆/ROT1 mutant. Furthermore, we investigated the consequences of restricted CaROT1 expression in C. albicans. We have shown that a low amount of Rot1 limits the transfer of oligosaccharide to protein, inhibits the activity of the first steps of oligosaccharide formation on dolichyl diphosphate, changes the composition of the cell wall, limits the protection of C. albicans against ER and abiotic stress, and finally prevents filamentation, which is an invasive structure of C. albicans