Candida albicans sphingolipid C9-methyltransferase is involved in hyphal elongation

Abstract

C9-methylated glucosylceramide is a fungus-specific sphingolipid. This lipid is a major membrane component in the cell and is thought to play important roles in the growth and virulence of several fungal species. To investigate the importance of the methyl branch of the long-chain base in glucosylceramides in pathogenic fungi, we identified and characterized a sphingolipid C9-methyltransferase gene (MTS1, C9-MethylTransferase forSphingolipid1) in the pathogenic yeastCandida albicans. Themts1disruptant lacked (E,E)-9-methylsphinga-4,8-dienine in its glucosylceramides and contained (E)-sphing-4-enine and (E,E)-sphinga-4,8-dienine. Reintroducing theMTS1gene into themts1disruptant restored the synthesis of (E,E)-9-methylsphinga-4,8-dienine in the glucosylceramides. We also created a disruptant of theHSX11gene, encoding glucosylceramide synthase, which catalyses the final step of glucosylceramide synthesis, inC. albicansand compared this mutant with themts1disruptant. TheC. albicans mts1andhsx11disruptants both had a decreased hyphal growth rate compared to the wild-type strain. Thehsx11disruptant showed increased susceptibility to SDS and fluconazole, similar to a previously reportedsld1disruptant that contained only (E)-sphing-4-enine in its glucosylceramides, suggesting that these strains have defects in their cell membrane structures. In contrast, themts1disruptant grew similarly to wild-type in medium containing SDS or fluconazole. These results suggest that the C9-methyl group of a long-chain base in glucosylceramides plays an important role in the hyphal elongation ofC. albicansindependent of lipid membrane disruption.