Abstract
Capsular polysaccharides are present in the outermost layer of the cell wall of Cryptococcus neoformans. The capsule consists of glucuronoxylomannan and glucuronoxylomannogalactan (GXMGal), both of which are major virulence factors that enable immune evasion. This study aimed to identify a novel glycosyltransferase involved in the biosynthesis of capsular polysaccharides in C. neoformans. While glucuronoxylomannan is the predominant capsule component and plays a broad role in immune evasion, GXMGal, despite its lower abundance, is thought to contribute to pathogenicity through its structurally unique galactomannan side chain. Glycosyltransferases involved in GXMGal biosynthesis have attracted much attention as potential targets for antifungal drug development because of their role in pathogenicity. In this study, we identified a novel β-galactoside α-(1 → 4)-mannosyltransferase, cryptococcal β-galactoside mannosyltransferase 1 (Cgm1) (glucan organizing enzyme 1 [Goe1]), which is involved in the biosynthesis of the galactomannan side chain of GXMGal. The GXMGal galactomannan side chain was almost completely lost in the cgm1 (goe1) disruptant, indicating that Cgm1 (Goe1) is the α-(1 → 4)-mannosyltransferase responsible for its biosynthesis. The cgm1 (goe1) disruptant exhibited temperature sensitivity at 37 °C. In addition, interferon-γ production was significantly increased in mice infected with the cgm1 (goe1) disruptant, demonstrating the importance of the galactomannan side chain of GXMGal in immune evasion.