REGULATION OF MANNITOL BIOSYNTHESIS AND DEGRADATION BY CRYPTOCOCCUS-NEOFORMANS

Cryptococcus neoformans, an encapsulated yeast that is an opportunisti c pathogen of AIDS patients, produced and secreted mannitol when incub ated with an appropriate carbon source. Glucose, fructose, and mannose were good growth substrates and were converted to mannitol. Maltose a nd xylose were good growth substrates but were not converted to mannit ol. Cells of C. neoformans that were grown on a non-mannitol-generatin g carbon source, such as peptone or xylose, were able to convert gluco se to mannitol only after a prolonged lag period in the presence of gl ucose. It was concluded that the enzymes of the mannitol biosynthetic pathway were not constitutively expressed but were induced in response to glucose or to a glucose metabolite. Enzymes required to catabolize mannitol, however, were constitutively expressed. The production of m annitol was inhibited by anaerobiosis, by the respiratory poison roten one, and by polyethylenesulfonate, a specific inhibitor of fungal NADP -dependent dehydrogenases. When cells were incubated with deuterated g lucose, the deuterium content of the mannitol produced,vas much lower than that of the glucose precursor, indicating that the glucose was di luted by an intracellular pool of an intermediate. We had previously s hown that C. neoformans contains a large intracellular pool of glucose 6-phosphate, and we now conclude that this pool of glucose 6-phosphat e is metabolically active.