Environmental Induction of White–Opaque Switching in Candida albicans

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Abstract
Candida albicans strains that are homozygous at the mating type locus (MTLa or MTLα) can spontaneously switch at a low frequency from the normal yeast cell morphology (white) to an elongated cell type (opaque), which is the mating-competent form of the fungus. The ability to switch reversibly between these two cell types also contributes to the pathogenicity of C. albicans, as white and opaque cells are differently adapted to specific host niches. We found that in strain WO-1, a strain in which genomic alterations have occurred, but not in other tested strains, switching from the white to the opaque phase can also be induced by environmental conditions. Transient incubation of white cells under anaerobic conditions programmed the cells to switch en masse to the opaque phase. The anaerobic induction of white–opaque switching was controlled by the transcription factor CZF1, which in heterozygous MTLa/α cells regulates filamentous growth under embedded, hypoxic conditions. Intriguingly, passage of white cells of strain WO-1 through the mouse intestine, a host niche in which the cells are likely to be exposed to anaerobic conditions, resulted in a strongly increased frequency of switching to the opaque phase. These results demonstrate that white–opaque switching is not only a spontaneous process but, in combination with genomic alterations, can also be induced by environmental signals, suggesting that switching and mating of C. albicans may occur with high efficiency in appropriate niches within its human host. Some strains of the opportunistic fungal pathogen Candida albicans can reversibly switch from the normal yeast morphology (white) to an elongated cell type termed opaque, which is the mating-competent form of C. albicans. C. albicans strains first have to become homozygous at the mating type locus to be able to switch to the usually less virulent opaque phase. As white–opaque switching occurs spontaneously only at a low frequency, the encounter of opaque cells of different strains and mating types is expected to be an extremely rare event and little recombination between strains occurs in nature. We found that genomic alterations may render white–opaque switching environmentally inducible in certain C. albicans strains. A transient incubation of such a strain under anaerobic conditions induced mass switching of white cells to the opaque phase, and this induction was mediated by the transcription factor Czf1p. Most strikingly, passage of white cells through the mammalian intestine, an environment in which the cells encounter anaerobic conditions, also stimulated switching to the opaque phase. Therefore, some strains of C. albicans may be induced to switch to the mating-competent opaque phase in response to environmental signals, giving them an opportunity for efficient genetic exchange in appropriate host niches.