Unusual effect of myo-inositol on phospholipid biosynthesis in Cryptococcus neoformans

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Abstract
Cryptococcus neoformansis an opportunistic fungal pathogen which preferentially localizes to the inositol-rich environment of the central nervous system. One of its distinguishing traits is its capacity to catabolize inositol. Inositol is a precursor for the synthesis of phosphatidylinositol (PI). This study demonstrated thatC. neoformanssynthesizes inositol. Three inositolcontaining sphingolipids were identified inC. neoformans:ceramide-(P-inositol)2mannose, ceramide-P-inositol-mannose, and ceramide-P-inositol. These inositol-containing sphingolipids are typical of fungi but not higher eukaryotes. The effect of inositol on the membrane lipid composition ofC. neoformanswas also examined. In contrast to the nonpathogenic yeastSaccharomyces cerevisiae, neither the PI composition nor the synthesis of methylated phospholipids was altered by exogenous inositol. Hence,C. neoformansappears to have a metabolic mechanism for maintaining a steady lipid composition regardless of the inositol in its environment.