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Serum inducesCandida albicans to make a rapid morphological change from the yeast cell form to hyphae. Contrary to the previous reports, we found that serum albumin does not play a critical role in this morphological change. Instead, a filtrate (molecular mass, &lt;1 kDa) devoid of serum albumin induces hyphae. To study genes controlling this response, we have isolated theRAS1 gene fromC. albicans by complementation. TheCandida Ras1 protein, like Ras1 and Ras2 ofSaccharomyces cerevisiae , has a long C-terminal extension. AlthoughRAS1 appears to be the onlyRAS gene present in theC. albicans genome, strains homozygous for a deletion ofRAS1 (ras1-2/ras1-3 ) are viable. The Candidaras1-2/ras1-3 mutant fails to form germ tubes and hyphae in response to serum or to a serum filtrate but does form pseudohyphae. Moreover, strains expressing the dominant activeRAS1V13 allele manifest enhanced hyphal growth, whereas those expressing a dominant negativeRAS1A16 allele show reduced hyphal growth. These data show that low-molecular-weight molecules in serum induce hyphal differentiation inC. albicans through a Ras-mediated signal transduction pathway.

Ras Signaling Is Required for Serum-Induced Hyphal Differentiation in Candida albicans