PHR1, A PH-REGULATED GENE OF CANDIDA-ALBICANS, IS REQUIRED FOR MORPHOGENESIS

Candida albicans, like many fungi, exhibits morphological plasticity, a property which may be related to its biological capacity as an oppor tunistic pathogen of humans. Morphogenesis and alterations in cell sha pe require integration of many cellular functions and occur in respons e to environmental signals, most notably PH aad temperature in the cas e of C. albicans. In the course of our studies of differential gene ex pression associated with dimorphism of C. albicans, we have isolated a gene, designated PHR1, which is regulated in response to the pH of th e culture medium. PHR1 expression was repressed at pH values below 5.5 and induced at more alkaline pH. The predicted amino acid sequence of the PHR1 protein was 56% identical to that of the Saccharomyces cerev isiae Ggp1/Gas1 protein, a highly glycosylated cell surface protein at tached to the membrane via glycosylphosphatidylinositol. A homozygous null mutant of PHR1 was constructed and found to exhibit a pH-conditio nal morphological defect. At alkaline pH, the mutant, unlike the paren tal type, was unable to conduct apical growth of either yeast or hypha l growth forms. This morphological aberration was not associated with defective cytoskeletal polarization or secretion. The results suggest that PHR1 defines a novel function required for apical cell growth and morphogenesis.