Abstract
Candida albicans strains that are homozygous at the mating type locus (MTL a 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 MTL a/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.
Highlights
The yeast Candida albicans is a member of the microbial flora of the gastrointestinal and urogenital tract in many healthy people, but it can cause serious infections when host defenses are compromised
We found that a transient incubation of white cells under anaerobic conditions resulted in mass switching to the opaque phase, which was mediated by the transcription factor Czf1p and depended on additional genomic alterations
In experiments aimed at elucidating the function of phasespecific genes we incubated strain WO-1, the MTLa strain in which white-opaque switching was originally discovered, and mutants derived from it on Lee’s agar plates at 25uC under anaerobic conditions
Summary
The yeast Candida albicans is a member of the microbial flora of the gastrointestinal and urogenital tract in many healthy people, but it can cause serious infections when host defenses are compromised. In response to environmental cues, e.g. the presence of serum, an increase in pH and temperature, or starvation conditions, C. albicans transitions from the budding yeast form to filamentous growth forms (true hyphae and pseudohyphae). This yeast-hyphal dimorphism, which includes dramatic alterations in the gene expression pattern, is important for the pathogenicity of C. albicans and mutants that are locked in the yeast or the filamentous form are attenuated for virulence [2,3]. The majority of C. albicans strains are MTLa/a heterozygous and produce the a1–a2 repressor, which is encoded by the two mating type loci and inhibits white-opaque switching. These strains can become MTL homozygous and switching-competent by loss of one homologue of the MTL carrying chromosome 5 and duplication of the remaining homologue or by mitotic recombination [7]
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