Regulation of Candida albicans Hyphal Morphogenesis by Endogenous Signals

Abstract

Candida albicans is a human commensal fungus that is able to assume several morphologies, including yeast, hyphal, and pseudohyphal. Under a range of conditions, C. albicans performs a regulated switch to the filamentous morphology, characterized by the emergence of a germ tube from the yeast cell, followed by a mold-like growth of branching hyphae. This transition from yeast to hyphal growth has attracted particular attention, as it has been linked to the virulence of C. albicans as an opportunistic human pathogen. Signal transduction pathways that mediate the induction of the hyphal transcription program upon the imposition of external stimuli have been extensively investigated. However, the hyphal morphogenesis transcription program can also be induced by internal cellular signals, such as inhibition of cell cycle progression, and conversely, the inhibition of hyphal extension can repress hyphal-specific gene expression, suggesting that endogenous cellular signals are able to modulate hyphal gene expression as well. Here we review recent developments in the regulation of the hyphal morphogenesis of C. albicans, with emphasis on endogenous morphogenetic signals.

Keywords: Candida albicans; cell cycle; hyphae; morphogenesis; transcription.

Figure 1

A simplified outline of one C. albicans hyphal morphogenesis signaling pathway.

Figure 2

Schematic depiction of some of the positive stimuli on hyphal induction (boxed in red and red arrows) and inhibitory signals (black). The cellular mediators of the hyphal morphogenetic pathways are depicted in yellow ovals and the transcription activators that induce hyphal growth are in orange ovals. The internal signals feeding back from the morphogenetic apparatus (dashed lines) and the cell cycle apparatus (solid lines) to the hypha-specific gene (HSG) expression program are shown in blue. See text for details of the individual interactions. The question mark indicates that it is still unclear whether Cdc42 affects the HSG expression directly or indirectly via its effect on the cytoskeleton.