Regulation of Candida albicans Hyphal Morphogenesis by Endogenous Signals.

Daniel Kornitzer

doi:10.3390/jof5010021

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.

Highlights

Candida albicans is a human commensal organism found in the gastrointestinal tract and other mucosal surfaces of a majority of the population [1,2,3]
In the United States, 9% of nosocomial bloodstream infections are caused by Candida spp. [5,6], of which 40%–70% are caused by C. albicans, and the rest by other Candida species [7,8]
Whereas a genomic screen to identify determinants of hyphal growth and/or virulence in mice revealed only a partial overlap [33], a more recent global analysis reaffirmed the link between hyphal morphogenesis and virulence by showing that among 177 mutant strains tested for virulence in mice, attenuation of virulence was significantly correlated with decreased hyphal morphogenesis [34]

Summary

Introduction

Candida albicans is a human commensal organism found in the gastrointestinal tract and other mucosal surfaces of a majority of the population [1,2,3] It can cause superficial mucosal infections in immunocompetent individuals, but among immunocompromised or debilitated patients, it can be responsible for life-threatening systemic disease [4]. These types are much more prevalent than systemic candidiasis and, usually less threatening than invasive disease, can impose a significant burden on patients [38] These superficial infections appear to involve the yeast-to-hyphal transition as well [39,40,41,42]

Mechanism of Hyphal Morphogenesis

Conclusions

Inhibition of Endocytosis Inhibits Hyphal Morphogenesis and HSG Expression

Positive Feedback Regulations of Hyphal Transcription

Findings

Reactive Oxygen and Nitrogen Species