N-acetyl-D-glucosamine-induced morphogenesis in Candida albicans

Abstract

N-acetylglucosamine is a morphogenic effector in the human pathogenic yeast Candida albicans. Depending on temperature, N-acetylglucosamine induces yeast-mycelial conversion or chlamydospore formation. N-acetylglucosamine is also a carbon source for growth in the yeast form. Germ-tube formation, i.e. the intermediary of yeast-mycelial conversion, is induced at temperatures in excess of 33 degrees C; at lower temperatures the yeast or the pseudomycelial form of the organism predominates. 2-Deoxyglucose, at concentrations which do not affect yeast growth, is a potent inhibitor of N-acetylglucosamine-induced germ-tube formation. N-acetylglucosamine suffices as both the inducer and the carbon sources for morphogenesis and both transcription and translation are required for the yeast to mycelial transition. The metabolism of N-acetylglucosamine is essentially the same for yeast phase cells (28 degrees C) and germ-tube forming cells (37 degrees C): enzymes for N-acetylglucosamine uptake and catabolism are equally well induced by gene expression at 28 degrees C and 37 degrees C. During germ-tube formation, the chitin content and the activity of the regulatory enzyme chitin synthase increase. Germ-tube formation in C. albicans can also be induced gratuitously by a number of N-acetylhexosamine derivatives (N-acetylglucosamine covalently linked to agarose, N-acetylmannosamine, hyaluronic acid, colloidal chitin, and mucin). These compounds are not taken up by the yeast cells and do not support growth which suggests that germ-tube formation is triggered by a cell-surface receptor mechanism. It is proposed that, after binding to the receptor, N-acetylglucosamine produces an intracellular message which primes the cell for morphogenesis. This message would ultimately be responsible for the choice of the mode of growth, spherical versus apical, that is characteristic of yeast or mycelial form.