Environmental Induction of White–Opaque Switching in Candida albicans

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.

The Evolution of Sex: a Perspective from the Fungal Kingdom

“…Thus, C. albicans, which is commonly resident on the mucosa of the mouth and oropharynx, gastrointestinal (GI) tract, and vagina might transiently be present in environments involving skin adjacent to these areas, undergo mating, and then either return to other niches in the same individual or be transmitted to another host. Similar studies have provided evidence that both anaerobic conditions and the elevated CO 2 levels found in the host can promote white-to-opaque switching and, thereby, mating (51,112,249). C. albicans mating might also occur and be promoted in the context of biofilms present on mucosal surfaces.…”

Stress-Induced Phenotypic Switching inCandida albicans

“…To determine the sensitivity of the switch to Wor1p levels, WOR1 copy number was manipulated in the SC5314 background. White-opaque switching has already been shown to be sensitive to WOR1 copy number in clinical isolates of C. albicans (Ramirez-Zavala et al, 2008).…”

“…Integration was checked using oligo pairs 52/55 and 54/56. CHY439 also was transformed with an ApaI/SacII fragment from pWOR1-3, a plasmid containing the WOR1 gene as well as ϳ9 kb of the WOR1 promoter (Ramirez-Zavala et al, 2008), a gift from Joachim Morschhauser (University of Wü rzburg, Wü rzburg, Germany). This yielded strains KAY314-17 containing three copies of the WOR1 gene, and integration was checked using oligos 61/62.…”

Candida albicans Czf1 and Efg1 Coordinate the Response to Farnesol during Quorum Sensing, White-Opaque Thermal Dimorphism, and Cell Death

“…A mechanism for triggering cell death within a subset of the Candida community, for example, within the matrix of a biofilm, could improve survival within a host. The observation that Czf1 and Efg1 play critical roles in both the response to farnesol and white-to-opaque cell switching is probably not a coincidence (21,22,(38)(39)(40), since both are also critical for biofilm formation (20,41). The hypothesis that intentional dysregulation of Efg1 and Czf1 occurs in biofilms is intriguing, particularly because of its implications for the maintenance of the persistence and virulence of C. albicans within the host.…”