Iron deprivation inducesEFG1-mediated hyphal development inCandida albicanswithout affecting biofilm formation

Abstract

In this study, we investigated the role of cellular iron status in hyphae and biofilm formation in Candida albicans. Iron deprivation by a chelator, bathophenanthrolene disulfonic acid, promoted hyphal development even in nonhyphal-inducing media without affecting growth of C. albicans cells. Iron-acquisition defective mutants, Deltaftr1 and Deltaccc2, also showed hyphal formation, which was prevented by iron supplementation. Notably, most of the tested morphological mutants Deltacph1, Deltaefh1 and Deltatpk1 continued to form hyphae under iron-deprived conditions, except the Deltaefg1 null mutant, which showed a complete block in hyphae formation. The role of EFG1 in filamentation under iron-deprived conditions was further confirmed by Northern analysis, which showed a considerable upregulation of the EFG1 transcript. Of notable importance, all the morphological mutants including Deltaefg1 mutant possessed enhanced membrane fluidity under iron-deprived conditions; however, this did not appear to contribute to hyphal development. Interestingly, iron deprivation did not affect the ability of C. albicans to form biofilms on the catheter surface and led to no gross defects in azole resistance phenotype of these biofilms of C. albicans cells. Our study, for the first time, establishes a link between cellular iron, Efg1p and hyphal development of C. albicans cells that is independent of biofilm formation.

Iron restriction-induced adaptations in the wall proteome of Candida albicans

“…However, the iron content was strongly diminished compared to the YPS control without BPS or even to a stationary-phase culture (Table 1). Another round of culturing in YPS+200 mM BPS (BPS-26) reduced the dry biomass by about 40 % (Table 1) and consistent with earlier observations (Hameed et al, 2008) hyphal development was strongly stimulated (data not shown). However, the total iron content (mg cell dry weight) 21 did not decrease any further, suggesting that during the first incubation in the presence of BPS all iron stores were depleted and that during the second incubation in the presence of BPS iron became growth-limiting.…”

“…However, Weissman & Kornitzer (2004) present quantitative data of haem-binding by iron-starved wildtype and mutant cells indicating that Rbt5 is the major contributor. Finally, Hyr1 and the ferritin receptor Als3 presumably increased in abundance during iron starvation since they are associated with hyphal growth (Almeida et al, 2008;Bailey et al, 1996), which is stimulated under low-iron conditions (Hameed et al, 2008;this paper).…”

Normal Adaptation of Candida albicans to the Murine Gastrointestinal Tract Requires Efg1p-Dependent Regulation of Metabolic and Host Defense Genes

“…An efg1 Ϫ null mutant was attenuated for virulence in a systemic model of candidiasis and was more susceptible to phagocytosis (17,30). Efg1p regulates gene expression in response to serum, temperature, hypoxia, and low iron availability and in kidney lesions (22,25,(31)(32)(33)(34). Therefore, Efg1p regulates a large number of genes encoding cell surface proteins, stress response proteins, and metabolic activities in response to various environmental cues.…”

“…Hyphal morphology is induced by an array of environmental signals which converge through a network of transcription factors, allowing C. albicans to fine-tune its responses to changes in the environment (19)(20)(21)(22)(23)(24).…”

Modulation of Morphogenesis in Candida albicans by Various Small Molecules

“…The cellular targets of these structurally different molecules are not known. In contrast, hydrogen peroxide and the iron chelator bathophenanthrolene disulfonic acid (BPS) both induced hyphal development in noninducing conditions (48,93). BPS promoted filamentation by increasing EFG1 mRNA levels.…”