GST2 is Required for Nitrogen Starvation-Induced Filamentous Growth in Candida albicans

2014 ◽  
Vol 24 (9) ◽  
pp. 1207-1215 ◽  
Author(s):  
So-Hyoung Lee ◽  
Soon-Chun Chung ◽  
Jongheon Shin ◽  
Ki-Bong Oh
Keyword(s):  
Candida Albicans ◽  
Nitrogen Starvation ◽  
Filamentous Growth

scholarly journals Control of Ammonium Permease Expression and Filamentous Growth by the GATA Transcription Factors GLN3 and GAT1 in Candida albicans

2007 ◽  
Vol 6 (5) ◽  
pp. 875-888 ◽  
Author(s):  
Neelam Dabas ◽  
Joachim Morschhäuser
Keyword(s):  
Candida Albicans ◽  
Transcription Factors ◽  
Nitrogen Starvation ◽  
Constitutive Expression ◽  
Filamentous Growth ◽  
Human Fungal Pathogen ◽  
Gata Transcription Factors ◽  
Important Regulator ◽  
Strain Sc5314 ◽  
Nitrogen Conditions

ABSTRACT In response to nitrogen starvation, the human fungal pathogen Candida albicans switches from yeast to filamentous growth. This morphogenetic switch is controlled by the ammonium permease Mep2p, whose expression is induced under limiting nitrogen conditions. In order to understand in more detail how nitrogen starvation-induced filamentous growth is regulated in C. albicans, we identified the cis-acting sequences in the MEP2 promoter that mediate its induction in response to nitrogen limitation. We found that two putative binding sites for GATA transcription factors have a central role in MEP2 expression, as deletion of the region containing these sites or mutation of the GATAA sequences in the full-length MEP2 promoter strongly reduced MEP2 expression. To investigate whether the GATA transcription factors GLN3 and GAT1 regulate MEP2 expression, we constructed mutants of the C. albicans wild-type strain SC5314 lacking one or both of these transcription factors. Expression of Mep2p was strongly reduced in gln3Δ and gat1Δ single mutants and abolished in gln3Δ gat1Δ double mutants. Deletion of GLN3 strongly inhibited filamentous growth under limiting nitrogen conditions, but the filamentation defect of gln3Δ mutants could be rescued by constitutive expression of MEP2 from the ADH1 promoter. In contrast, inactivation of GAT1 had no effect on filamentation, and we found that filamentation became independent of the presence of a functional MEP2 gene in the gat1Δ mutants, indicating that the loss of GAT1 function results in the activation of other pathways inducing filamentous growth. These results demonstrate that the GATA transcription factors GLN3 and GAT1 control expression of the MEP2 ammonium permease and that GLN3 is also an important regulator of nitrogen starvation-induced filamentous growth in C. albicans.

scholarly journals TUP1, CPH1 and EFG1 Make Independent Contributions to Filamentation in Candida albicans

Genetics ◽  
2000 ◽  
Vol 155 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Burkhard R Braun ◽  
Alexander D Johnson
Keyword(s):  
Candida Albicans ◽  
Environmental Conditions ◽  
Target Genes ◽  
Single Cells ◽  
Filamentous Growth ◽  
Surface Proteins ◽  
Pathway Expression ◽  
Separate Pathway ◽  
The Common ◽  
Growth Pathway

Abstract The common fungal pathogen, Candida albicans, can grow either as single cells or as filaments (hyphae), depending on environmental conditions. Several transcriptional regulators have been identified as having key roles in controlling filamentous growth, including the products of the TUP1, CPH1, and EFG1 genes. We show, through a set of single, double, and triple mutants, that these genes act in an additive fashion to control filamentous growth, suggesting that each gene represents a separate pathway of control. We also show that environmentally induced filamentous growth can occur even in the absence of all three of these genes, providing evidence for a fourth regulatory pathway. Expression of a collection of structural genes associated with filamentous growth, including HYR1, ECE1, HWP1, ALS1, and CHS2, was monitored in strains lacking each combination of TUP1, EFG1, and CPH1. Different patterns of expression were observed among these target genes, supporting the hypothesis that these three regulatory proteins engage in a network of individual connections to downstream genes and arguing against a model whereby the target genes are regulated through a central filamentous growth pathway. The results suggest the existence of several distinct types of filamentous forms of C. albicans, each dependent on a particular set of environmental conditions and each expressing a unique set of surface proteins.

scholarly journals Invasive Filamentous Growth ofCandida albicansIs Promoted by Czf1p-Dependent Relief of Efg1p-Mediated Repression

Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1749-1753 ◽  
Author(s):  
Angela D Giusani ◽  
Marcelo Vinces ◽  
Carol A Kumamoto
Keyword(s):  
Candida Albicans ◽  
Filamentous Growth ◽  
Environmental Cues ◽  
Complex Regulation

AbstractFilamentation of Candida albicans occurs in response to many environmental cues. During growth within matrix, Efg1p represses filamentation and Czf1p relieves this repression. We propose that Czf1p interacts with Efg1p, altering its function. The complex regulation of filamentation may reflect the versatility of C. albicans as a pathogen.

scholarly journals Identification and Characterization of TUP1-Regulated Genes in Candida albicans

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 31-44 ◽  
Author(s):  
Burkhard R Braun ◽  
W Steven Head ◽  
Ming X Wang ◽  
Alexander D Johnson
Keyword(s):  
Candida Albicans ◽  
Systemic Infection ◽  
Subtractive Hybridization ◽  
Filamentous Growth ◽  
Surface Proteins ◽  
Infection Model ◽  
Ferric Reductase ◽  
Pathogenesis Related Protein ◽  
Plant Pathogenesis ◽  
Rnase T2

Abstract TUP1 encodes a transcriptional repressor that negatively controls filamentous growth in Candida albicans. Using subtractive hybridization, we identified six genes, termed repressed by TUP1 (RBT), whose expression is regulated by TUP1. One of the genes (HWP1) has previously been characterized, and a seventh TUP1-repressed gene (WAP1) was recovered due to its high similarity to RBT5. These genes all encode secreted or cell surface proteins, and four out of the seven (HWP1, RBT1, RBT5, and WAP1) encode putatively GPI-modified cell wall proteins. The remaining three, RBT2, RBT4, and RBT7, encode, respectively, an apparent ferric reductase, a plant pathogenesis-related protein (PR-1), and a putative secreted RNase T2. The expression of RBT1, RBT4, RBT5, HWP1, and WAP1 was induced in wild-type cells during the switch from the yeast form to filamentous growth, indicating the importance of TUP1 in regulating this process and implicating the RBTs in hyphal-specific functions. We produced knockout strains in C. albicans for RBT1, RBT2, RBT4, RBT5, and WAP1 and detected no phenotypes on several laboratory media. However, two animal models for C. albicans infection, a rabbit cornea model and a mouse systemic infection model, revealed that rbt1Δ and rbt4Δ strains had significantly reduced virulence. TUP1 appears, therefore, to regulate many genes in C. albicans, a significant fraction of which are induced during filamentous growth, and some of which participate in pathogenesis.

scholarly journals CAP1, an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

2001 ◽  
Vol 183 (10) ◽  
pp. 3211-3223 ◽  
Author(s):  
Yong-Sun Bahn ◽  
Paula Sundstrom
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Germ Tube ◽  
Filamentous Growth ◽  
Tube Formation ◽  
Camp Signaling ◽  
Solid Media ◽  
Opportunistic Fungal Pathogen ◽  
Camp Levels

ABSTRACT In response to a wide variety of environmental stimuli, the opportunistic fungal pathogen Candida albicans exits the budding cycle, producing germ tubes and hyphae concomitant with expression of virulence genes, such as that encoding hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP) increases in promoting bud-hypha transitions, but genetic evidence relating genes that control cAMP levels to bud-hypha transitions has not been reported. Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with Ras and adenylate cyclase to increase cAMP levels under specific environmental conditions. To initiate studies on the relationship between cAMP signaling and bud-hypha transitions in C. albicans, we identified, cloned, characterized, and disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1 budded in conditions that led to germ tube formation in isogenic strains withCAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha transitions and filamentous growth in thecap1/cap1 mutant in liquid and solid media, respectively, showing clearly that cAMP promotes hypha formation in C. albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans strains with deletions of both alleles ofCAP1 were avirulent in a mouse model of systemic candidiasis. The avirulence of a germ tube-deficientcap1/cap1 mutant coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1-mediated cAMP signaling pathway is required for bud-hypha transitions, filamentous growth, and the pathogenesis of candidiasis.

scholarly journals Mitochondrial perturbation reduces susceptibility to xenobiotics through altered efflux in Candida albicans

Genetics ◽  
2021 ◽  
Author(s):  
Saif Hossain ◽  
Amanda O Veri ◽  
Zhongle Liu ◽  
Kali R Iyer ◽  
Teresa R O’Meara ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mitochondrial Function ◽  
Efflux Pump ◽  
Systemic Disease ◽  
Filamentous Growth ◽  
Hsp90 Inhibitor ◽  
Homozygous Deletion ◽  
Hsp90 Inhibitors ◽  
Hsp90 Inhibition ◽  
Conditional Expression

Abstract Candida albicans is a leading human fungal pathogen, which can cause superficial infections or life-threatening systemic disease in immunocompromised individuals. The ability to transition between yeast and filamentous forms is a major virulence trait of C. albicans, and a key regulator of this morphogenetic transition is the molecular chaperone Hsp90. To explore the mechanisms governing C. albicans morphogenesis in response to Hsp90 inhibition, we performed a functional genomic screen using the gene replacement and conditional expression (GRACE) collection to identify mutants that are defective in filamentation in response to the Hsp90 inhibitor, geldanamycin. We found that transcriptional repression of genes involved in mitochondrial function blocked filamentous growth in response to the concentration of Hsp90 inhibitor used in the screen, and this was attributable to increased resistance to the compound. Further exploration revealed that perturbation of mitochondrial function reduced susceptibility to two structurally distinct Hsp90 inhibitors, geldanamycin and radicicol, such that filamentous growth was restored in the mitochondrial mutants by increasing the compound concentration. Deletion of two representative mitochondrial genes, MSU1 and SHY1, enhanced cellular efflux and reduced susceptibility to diverse intracellularly acting compounds. Additionally, screening a C. albicans efflux pump gene deletion library implicated Yor1 in efflux of geldanamycin and Cdr1, in efflux of radicicol. Deletion of these transporter genes restored sensitivity to Hsp90 inhibitors in MSU1 and SHY1 homozygous deletion mutants, thereby enabling filamentation. Taken together, our findings suggest that mitochondrial dysregulation elevates cellular efflux and consequently reduces susceptibility to xenobiotics in C. albicans.

scholarly journals Activation of Rac1 by the Guanine Nucleotide Exchange Factor Dck1 Is Required for Invasive Filamentous Growth in the Pathogen Candida albicans

2008 ◽  
Vol 19 (9) ◽  
pp. 3638-3651 ◽  
Author(s):  
Hannah Hope ◽  
Stéphanie Bogliolo ◽  
Robert A. Arkowitz ◽  
Martine Bassilana
Keyword(s):  
Candida Albicans ◽  
G Proteins ◽  
Morphological Changes ◽  
Guanine Nucleotide Exchange Factor ◽  
Filamentous Growth ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor

Rho G proteins and their regulators are critical for cytoskeleton organization and cell morphology in all eukaryotes. In the opportunistic pathogen Candida albicans, the Rho G proteins Cdc42 and Rac1 are required for the switch from budding to filamentous growth in response to different stimuli. We show that Dck1, a protein with homology to the Ced-5, Dock180, myoblast city family of guanine nucleotide exchange factors, is necessary for filamentous growth in solid media, similar to Rac1. Our results indicate that Dck1 and Rac1 do not function in the same pathway as the transcription factor Czf1, which is also required for embedded filamentous growth. The conserved catalytic region of Dck1 is required for such filamentous growth, and in vitro this region directly binds a Rac1 mutant, which mimics the nucleotide-free state. In vivo overexpression of a constitutively active Rac1 mutant, but not wild-type Rac1, in a dck1 deletion mutant restores filamentous growth. These results indicate that the Dock180 guanine nucleotide exchange factor homologue, Dck1 activates Rac1 during invasive filamentous growth. We conclude that specific exchange factors, together with the G proteins they activate, are required for morphological changes in response to different stimuli.

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