Factors affecting filamentation in Candida albicans: relationship of the uptake and distribution of proline to morphogenesis.

When glucose was present in high concentration, Candida albicans formed filaments in a phosphate-buffered medium, regardless of the nitrogen source. In lower concentrations of glucose, filamentation occurred only when various members of the glutamate, succinyl, or acetoacetyl-coenzyme A families of amino acids were used as sole nitrogen sources. Yeast morphology could be maintained either by replacing the amino acids in the medium with ammonium chloride or by making the medium high in phosphate or biotin. Studies using [U-14C]proline indicated that proline was catabolized in a manner consistent with the generation of increased cellular reducing potential and that the proline label entered into the Kreb's cycle. A reduction in Kreb's cycle activity was evidenced by an initial increase and then a rapid drop of the total organic acid content of the cells as well as in specific Kreb's cycle intermediates. Filamentation under conditions of low phosphate, high glucose, and increased cellular reduction potential, accompanied by a decrease in Kreb's cycle activity, suggests that morphogenesis in C. albicans is correlated with a Crabtree-like effect, i.e., repression of mitochondrial activity.