The MAP kinase Hog1p differentially regulates stress-induced production and accumulation of glycerol and d-arabitol in Candida albicans

Candida albicans produces and accumulates large amounts of the polyols d-arabitol and glycerol in culture, and/or in infected mammalian tissues. However, the effects of environmental stresses on production and accumulation of these polyols, and the means by which polyol production and accumulation are regulated have not been studied. C. albicans grown in glucose at 30 degrees C (i) produced maximal amounts of glycerol within 6 h, (ii) produced maximal amounts of d-arabitol and ribitol within 12 h, and (iii) released most of these polyols into the extracellular environment. C. albicans responded to osmotic and citric acid stress by producing and accumulating more glycerol, and to temperature and oxidative stresses by producing more d-arabitol. The increase in intracellular glycerol was proportional to extracellular osmolarity, suggesting that glycerol functions as an osmolyte. The MAP kinase Hog1p is required for wild-type glycerol production in several fungal species subjected to osmotic stress, but it is not known if Hog1p plays a role in regulating d-arabitol production. Therefore, two C. albicans hog1 null mutants were constructed and tested for the ability to produce glycerol and d-arabitol in response to environmental stresses. The ability to grow and produce glycerol when exposed to osmotic or citric acid stresses, and to produce d-arabitol when exposed to oxidative stress, was partially dependent on Hog1p, but the ability to produce d-arabitol when exposed to temperature stress was Hog1p independent. These results imply that multiple pathways regulate glycerol and d-arabitol synthesis in C. albicans.