A second high-frequency switching system was identified in selected pathogenic strains in the dimorphic yeast Candida albicans. In the characterized strain WO-1, cells switched heritably, reversibly, and at a high frequency (-10-2) between two phenotypes readily distinguishable by the size, shape, and color of colonies formed on agar at 25°C. In this system, referred to as the "white-opaque transition," cells formed either "white" hemispherical colonies, which were similar to the ones formed by standard laboratory strains of C. albicans, or "opaque" colonies, which were larger, flatter, and grey. At least three other heritable colony phenotypes were generated by WO-1 and included one irregular-wrinkle and two fuzzy colony phenotypes. The basis of the white-opaque transition appears to be a fundamental difference in cellular morphology. White cells were similar in shape, size, and budding pattern to cells of common laboratory strains. In dramatic contrast, opaque cells were bean shaped and exhibited three times the volume and twice the mass of white cells, even though these alternative phenotypes contained the same amount of DNA and a single nucleus in the log phase. In addition to differences in morphology, white and opaque cells differed in their generation time, in their sensitivity to low and high temperatures, and in their capacity to form hypae. The possible molecular mechanisms involved in high-frequency switching in the white-opaque transition are considered.Recently, we demonstrated that a common laboratory strain of the dimorphic yeast Candida albicans was capable of switching heritably, reversibly, and at a high frequency among at least seven general phenotypes distinguishable by colony morphology (17; D. R. Soll, B. Slutsky, S. Mackenzie, C. Langtimm, and M. Staebell, J. Oral Pathol., in press). In this system, cells of the parent strain switched spontaneously at a frequency of roughly io-4. A low dose of UV light, which killed less than 10% of the cell population, stimulated a 200-fold increase in this initial frequency. Whether spontaneous or UV induced, once the original strain switched, it continued to switch spontaneously and reversibly between variant colony phenotypes at a frequency of 10-2. Revertants to the original colony phenotype which exhibited a decrease in switching frequency from 10-2 to i0' were also obtained (17; Soll et al., in press).In examining the switching capabilities of strains of C. albicans isolated from patients with systemic infections, we have discovered a second switching system, which we will refer to as the "white-opaque transition." In this system, cells switch heritably, at a high frequency, and reversibly between two phenotypes which generate alternative colony morphologies distinguishable by colony size, shape, and color. In the "white" phenotype, cells form colonies which are white and hemispherical. In the "opaque" phenotype, cells form colonies which are larger, flatter, and opaque, or grey. The differences in colony shape and tone appear to be the result of a...

The pathogenic yeast Candida albicans switches heritably and at high frequency between at least seven general phenotypes identified by colony morphology on agar. Spontaneous conversion from the original smooth to variant phenotypes (star, ring, irregular wrinkle, hat, stipple, and fuzzy) occurs at a combined frequency of 1.4 X 10(-4), but is increased 200 times by a low dose of ultraviolet light that kills less than 10 percent of the cells. After the initial conversion, cells switch spontaneously to other phenotypes at a combined frequency of 2 X 10(-2). Switching is therefore heritable, but also reversible at high frequency. The genetic basis of this newly discovered process and its possible role in Candida pathogenesis are considered.

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