Disruption of the sphingolipid Δ8-desaturase gene causes a delay in morphological changes in Candida albicans

Abstract

Ceramides and glycosylceramides, including desaturated long-chain bases, are present in most fungi as well as animals and plants. However, as the budding yeast Saccharomyces cerevisiae is not capable of desaturating long-chain bases, little is known about the physiological roles of these compounds in fungi. To investigate the necessity of desaturation of long-chain backbones in ceramides and glucosylceramides in fungal cells, we have identified and characterized a sphingolipid D 8-desaturase (SLD) gene from the pathogenic yeast Candida albicans. Gene disruption of the C. albicans SLD homologue led to the accumulation of (E)-sphing-4-enine, a main substrate for the SLD enzyme. Introducing the Candida SLD gene homologue into these mutant cells resulted in the recovery of synthesis of (4E, 8E)-sphinga-4,8-dienine and this gene homologue was therefore identified as a Ca-SLD gene. Additionally, the sld disruptant of C. albicans had a decreased hyphal growth rate compared with the wild-type strain. These results suggest that D 8 -desaturation of long-chain bases in ceramides plays a role in the morphogenesis of C. albicans.

Insights into the phylogenetic and molecular evolutionary histories of Fad and Elovl gene families in Actiniaria

“…These structural characteristics include an N‐terminal cytochrome b5‐like binding domain (cyt‐b5; PF00173), which contains a hem binding motif (HPGG), and a fatty acid desaturase domain (FA_desaturase; PF00487), which contains three histidine boxes (HXXXH, HXXXHH, and QXXHH). To date, these sphingolipid desaturases have been identified in plants, such as Arabidopsis thaliana and B. officinalis , and fungi such as Candida albicans and Kluyveromyces lactis (Libisch, Michaelson, Lewis, Shewry, & Napier, 2000; Oura & Kajiwara, 2008; Sperling, Libisch, Zähringer, Napier, & Heinz, 2001; Sperling, Zähringer, & Heinz, 1998; Takakuwa, Kinoshita, Oda, & Ohnishi, 2002). Previous phylogenetic studies (Feng et al., 2017; Gostinčar, Turk, & Gunde‐Cimerman, 2010; Meesapyodsuk & Qiu, 2012) have shown that the paralogs of the genes encoding Fads and sphingolipid desaturases cluster together, as opposed to their respective orthologs.…”

Quality Control of Fungus-specific Glucosylceramide in Cryptococcus neoformans by Endoglycoceramidase-related Protein 1 (EGCrP1)

“…This notion is supported by previous findings. Immature forms of GlcCer (d18:0, d18:1, and d18:2) were generated when GCS-1 was overexpressed in yeasts (17), an immature GlcCer possessing d18:2 was generated in sphingolipid 9-methyltransferase-disrupted Pichia pastoris, C. albicans, and Fusarium graminearum (4,8,15,52), and GlcCer possessing d18:1 was generated in sphingolipid ⌬8-desaturase-disrupted P. pastoris and C. albicans (4,7).…”

“…gus-specific GlcCer (7,9,15). Sphingolipid ⌬4-desaturase and 9-methyltransferase utilize ceramide, but not GlcCer, as an acceptor substrate (8,18).…”

“…In addition to its pathogenicity, mature GlcCer is related to various biological events such as budding and cell division (10 -12), alkali tolerance (13,14), hyphal elongation (15), and plant defensin sensitivity (16). Immature GlcCer possessing a non-methylated d18:1 or d18:2 sphingoid base could not compensate for the functions of mature GlcCer (7,9,15).…”

“…Over the past decade, extensive studies have identified the enzymes involved in the biosynthesis of fungus-specific GlcCer. Dihydrosphingosine is acylated by ceramide synthase to form dihydroceramide (4), which is then modified by various enzymes, including fatty acid 2-hydroxylase (5), sphingolipid ⌬4-desaturase (6), sphingolipid ⌬8-desaturase (7), and sphingolipid 9-methyltransferase (8), generating a mature form of ceramide composed of a methyl d18:2 sphingoid base and an amide-linked ␣-hydroxy 16:0/18:0 fatty acid (see Fig. 7).…”