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

Cryptococcus neoformans is 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 that C. neoformans synthesizes inositol. Three inositol-containing sphingolipids were identified in C. neoformans: ceramide-(P-inositol)2mannose, mannose, 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 of C. neoformans was also examined. In contrast to the nonpathogenic yeast Saccharomyces cerevisiae, neither the PI composition nor the synthesis of methylated phospholipids was altered by exogenous inositol. Hence, C. neoformans appears to have a metabolic mechanism for maintaining a steady lipid composition regardless of the inositol in its environment.