Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans

Abstract

SUMMARY Candida albicans is an opportunistic fungal pathogen that is found in the normal gastrointestinal flora of most healthy humans. However, under certain environmental conditions, it can become a life-threatening pathogen. The shift from commensal organism to pathogen is often correlated with the capacity to undergo morphogenesis. Indeed, under certain conditions, including growth at ambient temperature, the presence of serum or N-acetylglucosamine, neutral pH, and nutrient starvation, C. albicans can undergo reversible transitions from the yeast form to the mycelial form. This morphological plasticity reflects the interplay of various signal transduction pathways, either stimulating or repressing hyphal formation. In this review, we provide an overview of the different sensing and signaling pathways involved in the morphogenesis and pathogenesis of C. albicans. Where appropriate, we compare the analogous pathways/genes in Saccharomyces cerevisiae in an attempt to highlight the evolution of the different components of the two organisms. The downstream components of these pathways, some of which may be interesting antifungal targets, are also discussed.

A comprehensive functional portrait of two heat shock factor-type transcriptional regulators involved in Candida albicans morphogenesis and virulence

“…albicans adaptation to temperature variation is one of the major critical traits of its ability to cause disease or to act as a commensal of warm-blooded species, as a temperature increase triggers hyphal development [2]. To date, three temperature-responsive transcription factors have been shown to play a role in C. albicans morphogenesis, Hsf1p [62,63], Sfl2p [39,40] and Hms1p [49].…”

“…The yeast-to-hyphae transition is triggered by a variety of environmental stimuli including nutrient availability, temperature, pH, CO 2 and serum [9][10][11][12][13]. This process correlates with the coordinated expression of a set of hyphal-specific genes (HSGs) with roles in orchestrating hyphal development.…”

“…The success of C. albicans as a major fungal pathogen of humans relies on a number of pathogenic traits, among which its capacity to grow and switch between at least three distinctive morphological forms: budding yeast, pseudohyphae and hyphae [2][3][4][5]. The morphogenetic transition has been commonly described as a critical trait for survival and virulence in the host, even though the analysis of a wide array of C. albicans knock-out mutants suggests that pathogenesis can be dissociated to some extent from morphological switching [6][7][8].…”

Candida albicansdimorphism as a therapeutic target

“…There are numerous publications that deal with the morphological switch from yeast-to-hyphal growth and the multiple factors that regulate this process, such as Ras1, Efg1, Cph1, Tec1 and Rim101 (reviewed in [6,7]). Less attention has been paid to factors that regulate the hyphal-to-yeast transition, such as the hyphal repressors Nrg1 or Tup1 [31][32][33], or to factors that are important for maintenance or extension of hyphal growth, for example Cln1, Pes1, Eed1 or Ume6 [34][35][36][37][38].…”

“…The fungus can also form chlamydospores, spore-like structures, produced under distinct conditions, of as yet unknown biological function [2,3], and undergo phenotypic switching between white and opaque morphologies -an event which is important for mating and biofilm formation [4,5]. The transition between yeast and hyphal growth (named dimorphism) is tightly regulated by a network of signal transduction pathways in response to environmental stimuli (reviewed in [6][7][8][9]). …”