Candida albicans White and Opaque Cells Undergo Distinct Programs of Filamentous Growth

Abstract

The ability to switch between yeast and filamentous forms is central to Candida albicans biology. The yeast-hyphal transition is implicated in adherence, tissue invasion, biofilm formation, phagocyte escape, and pathogenesis. A second form of morphological plasticity in C. albicans involves epigenetic switching between white and opaque forms, and these two states exhibit marked differences in their ability to undergo filamentation. In particular, filamentous growth in white cells occurs in response to a number of environmental conditions, including serum, high temperature, neutral pH, and nutrient starvation, whereas none of these stimuli induce opaque filamentation. Significantly, however, we demonstrate that opaque cells can undergo efficient filamentation but do so in response to distinct environmental cues from those that elicit filamentous growth in white cells. Growth of opaque cells in several environments, including low phosphate medium and sorbitol medium, induced extensive filamentous growth, while white cells did not form filaments under these conditions. Furthermore, while white cell filamentation is often enhanced at elevated temperatures such as 37°C, opaque cell filamentation was optimal at 25°C and was inhibited by higher temperatures. Genetic dissection of the opaque filamentation pathway revealed overlapping regulation with the filamentous program in white cells, including key roles for the transcription factors EFG1, UME6, NRG1 and RFG1. Gene expression profiles of filamentous white and opaque cells were also compared and revealed only limited overlap between these programs, although UME6 was induced in both white and opaque cells consistent with its role as master regulator of filamentation. Taken together, these studies establish that a program of filamentation exists in opaque cells. Furthermore, this program regulates a distinct set of genes and is under different environmental controls from those operating in white cells.

A Novel Function for Hog1 Stress-Activated Protein Kinase in Controlling White-Opaque Switching and Mating in Candida albicans

“…For example, under conditions of various environmental signals, the yeast forms of C. albicans can switch to filamentous cells (4)(5)(6)(7)(8). The reversible yeast-hypha transition regulated by a core set of transcription factors that mediate its developmental program is complex (7,(9)(10)(11)(12)(13). Hyphal formation also plays a major role in biofilm formation, which is closely linked with the propensity to cause infection and is associated with antifungal resistance (14)(15)(16).…”

Phosphate Starvation in Fungi Induces the Replacement of Phosphatidylcholine with the Phosphorus-Free Betaine Lipid Diacylglyceryl- N , N , N -Trimethylhomoserine

“…albicans can grow and be propagated as epigenetically distinct white-or opaque-phase cells, and an additional recent study (41) showed that opaque-phase C. albicans colonies can also assume a hyphal form under conditions of P i limitation, unlike white-phase cells, which (at least in the canonical laboratory isolates commonly used for physiological studies, such as strain SC5314) are not typically induced to express a hyphal phenotype with P i starvation as the sole nutrient limitation. The observed induction of hyphal morphogenesis by P i starvation in C. albicans opaque cells (but not white cells) may also be related to previous work on gene expression patterns in white versus opaque cells.…”

Comparative Evolution of Morphological Regulatory Functions in Candida Species

“…In this respect, C. albicans, which has retained the starvation response but also acquired the ability to robustly filament under a variety of nutrient-rich conditions, appears to be better adapted for colonization and infection of a wider range of host niches. A recent report that C. albicans opaque cells, which are mating competent, can undergo filamentation in response to distinct environmental cues also suggests that C. albicans further evolved cell type-specific filamentation for particular host niches (74).…”