scholarly journals Depletion of the Cullin Cdc53p Induces Morphogenetic Changes in Candida albicans

2009 ◽  
Vol 8 (5) ◽  
pp. 756-767 ◽  
Author(s):  
Katharina Trunk ◽  
Patrick Gendron ◽  
André Nantel ◽  
Sébastien Lemieux ◽  
Terry Roemer ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Essential Gene ◽  
Hyphal Growth ◽  
Growth Mode ◽  
Environmental Signals ◽  
Human Fungal Pathogen ◽  
Ubiquitin Ligase Complex ◽  
A Genome ◽  
Ubiquitination Pathway ◽  
Systemic Infections

ABSTRACT Candida albicans is an important opportunistic human fungal pathogen that can cause both mucosal and systemic infections in immunocompromised patients. Critical for the virulence of C. albicans is its ability to undergo a morphological transition from yeast to hyphal growth mode. Proper induction of filamentation is dependent on the ubiquitination pathway, which targets proteins for proteasome-mediated protein degradation or activates them for signaling events. In the present study, we evaluated the role of ubiquitination in C. albicans by impairing the function of the major ubiquitin-ligase complex SCF. This was done by depleting its backbone, the cullin Cdc53p (orf19.1674), using a tetracycline downregulatable promoter system. Cdc53p-depleted cells displayed an invasive phenotype and constitutive filamentation under conditions favoring yeast growth mode, both on solid and in liquid media. In addition, these cells exhibited an early onset of cell death, as judged from propidium iodide staining, suggesting that CDC53 is an essential gene in C. albicans. To identify Cdc53p-dependent pathways in C. albicans, a genome-wide expression analysis was carried out that revealed a total of 425 differentially expressed genes (fold change, ≥2; P ≤ 0.05) with 192 up- and 233 downregulated genes in the CDC53-repressed mutant compared to the control strain. GO term analysis identified biological processes significantly affected by Cdc53p depletion, including amino acid starvation response, with 14 genes being targets of the transcriptional regulator Gcn4p, and reductive iron transport. These results indicate that Cdc53p enables C. albicans to adequately respond to environmental signals.

scholarly journals Deletion of the CaBIG1 Gene Reduces β-1,6-Glucan Synthesis, Filamentation, Adhesion, and Virulence in Candida albicans

2006 ◽  
Vol 74 (4) ◽  
pp. 2373-2381 ◽  
Author(s):  
Takashi Umeyama ◽  
Aki Kaneko ◽  
Hiroshi Watanabe ◽  
Asuka Hirai ◽  
Yoshimasa Uehara ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Hyphal Growth ◽  
Wild Type ◽  
Environmental Signals ◽  
Human Fungal Pathogen ◽  
Functional Homolog ◽  
Solid Agar ◽  
Adhesion Failure ◽  
Specific Localization ◽  
Glucan Synthesis

ABSTRACT The human fungal pathogen Candida albicans is able to change its shape in response to various environmental signals. We analyzed the C. albicans BIG1 homolog, which might be involved in β-1,6-glucan biosynthesis in Saccharomyces cerevisiae. C. albicans BIG1 is a functional homolog of an S. cerevisiae BIG1 gene, because the slow growth of an S. cerevisiae big1 mutant was restored by introduction of C. albicans BIG1. CaBig1p was expressed constitutively in both the yeast and hyphal forms. A specific localization of CaBig1p at the endoplasmic reticulum or plasma membrane similar to the subcellular localization of S. cerevisiae Big1p was observed in yeast form. The content of β-1,6-glucan in the cell wall was decreased in the Cabig1Δ strain in comparison with the wild-type or reconstituted strain. The C. albicans BIG1 disruptant showed reduced filamentation on a solid agar medium and in a liquid medium. The Cabig1Δ mutant showed markedly attenuated virulence in a mouse model of systemic candidiasis. Adherence to human epithelial HeLa cells and fungal burden in kidneys of infected mice were reduced in the Cabig1Δ mutant. Deletion of CaBIG1 abolished hyphal growth and invasiveness in the kidneys of infected mice. Our results indicate that adhesion failure and morphological abnormality contribute to the attenuated virulence of the Cabig1Δ mutant.

scholarly journals Induction of theCandida albicansFilamentous Growth Program by Relief of Transcriptional Repression: A Genome-wide Analysis

2005 ◽  
Vol 16 (6) ◽  
pp. 2903-2912 ◽  
Author(s):  
David Kadosh ◽  
Alexander D. Johnson
Keyword(s):  
Candida Albicans ◽  
Transcriptional Repression ◽  
Fungal Pathogen ◽  
Morphological Transition ◽  
Whole Genome ◽  
Transcriptional Repressors ◽  
Genome Wide Analysis ◽  
Human Fungal Pathogen ◽  
Genome Wide ◽  
A Genome

Candida albicans, the major human fungal pathogen, undergoes a reversible morphological transition from blastospores (round budding cells) to filaments (elongated cells attached end-to-end). This transition, which is induced upon exposure of C. albicans cells to a number of host conditions, including serum and body temperature (37°C), is required for virulence. Using whole-genome DNA microarray analysis, we describe 61 genes that are significantly induced (≥2-fold) during the blastospore to filament transition that takes place in response to exposure to serum and 37°C. We next show that approximately half of these genes are transcriptionally repressed in the blastospore state by three transcriptional repressors, Rfg1, Nrg1, and Tup1. We conclude that the relief of this transcriptional repression plays a key role in bringing the C. albicans filamentous growth program into play, and we describe the framework of this transcriptional circuit.

scholarly journals Cell Cycle Dynamics and Quorum Sensing in Candida albicans Chlamydospores Are Distinct from Budding and Hyphal Growth

2005 ◽  
Vol 4 (7) ◽  
pp. 1191-1202 ◽  
Author(s):  
Stephen W. Martin ◽  
Lois M. Douglas ◽  
James B. Konopka
Keyword(s):  
Candida Albicans ◽  
Quorum Sensing ◽  
Hyphal Growth ◽  
Distinct Type ◽  
Positive Role ◽  
Human Fungal Pathogen ◽  
Morphological Defects ◽  
Greater Curvature ◽  
Cell Cycle Dynamics ◽  
Suspensor Cells

ABSTRACT The regulation of morphogenesis in the human fungal pathogen Candida albicans is under investigation to better understand how the switch between budding and hyphal growth is linked to virulence. Therefore, in this study we examined the ability of C. albicans to undergo a distinct type of morphogenesis to form large thick-walled chlamydospores whose role in infection is unclear, but they act as a resting form in other species. During chlamydospore morphogenesis, cells switch to filamentous growth and then develop elongated suspensor cells that give rise to chlamydospores. These filamentous cells were distinct from true hyphae in that they were wider and were not inhibited by the quorum-sensing factor farnesol. Instead, farnesol increased chlamydospore production, indicating that quorum sensing can also have a positive role. Nuclear division did not occur across the necks of chlamydospores, as it does in budding. Interestingly, nuclei divided within the suspensor cells, and then one daughter nucleus subsequently migrated into the chlamydospore. Septins were not detected near mitotic nuclei but were localized at chlamydospore necks. At later stages, septins localized throughout the chlamydospore plasma membrane and appeared to form long filamentous structures. Deletion of the CDC10 or CDC11 septins caused greater curvature of cells growing in a filamentous manner and morphological defects in suspensor cells and chlamydospores. These studies identify aspects of chlamydospore morphogenesis that are distinct from bud and hyphal morphogenesis.

scholarly journals PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis.

1995 ◽  
Vol 15 (2) ◽  
pp. 601-613 ◽  
Author(s):  
S M Saporito-Irwin ◽  
C E Birse ◽  
P S Sypherd ◽  
W A Fonzi
Keyword(s):  
Candida Albicans ◽  
Apical Cell ◽  
Protein A ◽  
Surface Protein ◽  
Hyphal Growth ◽  
Morphological Plasticity ◽  
Opportunistic Pathogen ◽  
Predicted Amino Acid Sequence ◽  
Alkaline Ph ◽  
Environmental Signals

Candida albicans, like many fungi, exhibits morphological plasticity, a property which may be related to its biological capacity as an opportunistic pathogen of humans. Morphogenesis and alterations in cell shape require integration of many cellular functions and occur in response to environmental signals, most notably pH and temperature in the case of C. albicans. In the course of our studies of differential gene expression associated with dimorphism of C. albicans, we have isolated a gene, designated PHR1, which is regulated in response to the pH of the culture medium. PHR1 expression was repressed at pH values below 5.5 and induced at more alkaline pH. The predicted amino acid sequence of the PHR1 protein was 56% identical to that of the Saccharomyces cerevisiae Ggp1/Gas1 protein, a highly glycosylated cell surface protein attached to the membrane via glycosylphosphatidylinositol. A homozygous null mutant of PHR1 was constructed and found to exhibit a pH-conditional morphological defect. At alkaline pH, the mutant, unlike the parental type, was unable to conduct apical growth of either yeast or hyphal growth forms. This morphological aberration was not associated with defective cytoskeletal polarization or secretion. The results suggest that PHR1 defines a novel function required for apical cell growth and morphogenesis.

scholarly journals Recent advances in understanding Candida albicans hyphal growth

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 700 ◽  
Author(s):  
Robert A. Arkowitz ◽  
Martine Bassilana
Keyword(s):  
Candida Albicans ◽  
Medical Research ◽  
Filamentous Fungi ◽  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Morphological Changes ◽  
Hyphal Growth ◽  
Yeast Form ◽  
Intensive Research ◽  
Human Fungal Pathogen

Morphological changes are critical for the virulence of a range of plant and human fungal pathogens. Candida albicans is a major human fungal pathogen whose ability to switch between different morphological states is associated with its adaptability and pathogenicity. In particular, C. albicans can switch from an oval yeast form to a filamentous hyphal form, which is characteristic of filamentous fungi. What mechanisms underlie hyphal growth and how are they affected by environmental stimuli from the host or resident microbiota? These questions are the focus of intensive research, as understanding C. albicans hyphal growth has broad implications for cell biological and medical research.

scholarly journals Pseudohyphal Regulation by the Transcription Factor Rfg1p in Candida albicans

2010 ◽  
Vol 9 (9) ◽  
pp. 1363-1373 ◽  
Author(s):  
Ian A. Cleary ◽  
Priyadarshini Mulabagal ◽  
Sara M. Reinhard ◽  
Nishant P. Yadev ◽  
Craig Murdoch ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Pcr Analysis ◽  
Yeast Growth ◽  
Content Type ◽  
Human Fungal Pathogen ◽  
Hypha Formation

ABSTRACT The opportunistic human fungal pathogen Candida albicans is a major cause of nosocomial infections. One of the fundamental features of C. albicans pathogenesis is the yeast-to-hypha transition. Hypha formation is controlled positively by transcription factors such as Efg1p and Cph1p, which are required for hyphal growth, and negatively by Tup1p, Rfg1p, and Nrg1p. Previous work by our group has shown that modulating NRG1 gene expression, hence altering morphology, is intimately linked to the capacity of C. albicans to cause disease. To further dissect these virulence mechanisms, we employed the same strategy to analyze the role of Rfg1p in filamentation and virulence. Studies using a tet-RFG1 strain revealed that RFG1 overexpression does not inhibit hypha formation in vitro or in the mouse model of hematogenously disseminated candidiasis. Interestingly, RFG1 overexpression drives formation of pseudohyphae under yeast growth conditions—a phenotype similar to that of C. albicans strains with mutations in one of several mitotic regulatory genes. Complementation assays and real-time PCR analysis indicate that, although the morphology of the tet-RFG1 strain resembles that of the mitotic regulator mutants, Rfg1p overexpression does not impact expression of these genes.

scholarly journals Alternative oxidase induction protects Candida albicans from respiratory stress and promotes hyphal growth

2018 ◽  
Author(s):  
Lucian Duvenage ◽  
Louise A. Walker ◽  
Aleksandra Bojarczuk ◽  
Simon A. Johnston ◽  
Donna M. McCallum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Alternative Oxidase ◽  
Hyphal Growth ◽  
Infection Model ◽  
Human Fungal Pathogen ◽  
Zebrafish Infection

AbstractThe human fungal pathogenCandida albicanspossesses two genes expressing a cyanide-insensitive Alternative Oxidase (Aox) enzymes in addition to classical and parallel electron transfer chains (ETC). In this study, we examine the role of Aox inC.albicansunder conditions of respiratory stress, which may be inflicted during its interaction with the human host or co-colonising bacteria. We find that the level of Aox expression is sufficient to modulate resistance to classical ETC inhibition under respiratory stress and are linked to gene expression changes that can promote both survival and pathogenicity. For example we demonstrate that Aox function is important for the regulation of filamentation inC.albicansand observe that cells lacking Aox function lose virulence in a zebrafish infection model. Our investigations also identify that pyocyanin, a phenazine produced by the co-colonising bacteriumPseudomonas aeruginosa, inhibits Aox-based respiration inC.albicans. These results suggest that Aox plays important roles within respiratory stress response pathways whichC.albicansmay utilise both as a commensal organism and as a pathogen.

scholarly journals Transcriptional control of hyphal morphogenesis in Candida albicans

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sonia Villa ◽  
Mohammad Hamideh ◽  
Anthony Weinstock ◽  
Mohammad N Qasim ◽  
Tony R Hazbun ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Transcriptional Control ◽  
Transcriptional Regulatory Network ◽  
Hyphal Growth ◽  
Vital Role ◽  
Environmental Cues ◽  
Environmental Signals ◽  
Hyphal Morphogenesis ◽  
Transcriptional Regulatory ◽  
Opportunistic Fungal Pathogen

ABSTRACT Candida albicans is a multimorphic commensal organism and opportunistic fungal pathogen in humans. A morphological switch between unicellular budding yeast and multicellular filamentous hyphal growth forms plays a vital role in the virulence of C. albicans, and this transition is regulated in response to a range of environmental cues that are encountered in distinct host niches. Many unique transcription factors contribute to the transcriptional regulatory network that integrates these distinct environmental cues and determines which phenotypic state will be expressed. These hyphal morphogenesis regulators have been extensively investigated, and represent an increasingly important focus of study, due to their central role in controlling a key C. albicans virulence attribute. This review provides a succinct summary of the transcriptional regulatory factors and environmental signals that control hyphal morphogenesis in C. albicans.

scholarly journals Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in Candida albicans

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Sophia Ruben ◽  
Enrico Garbe ◽  
Selene Mogavero ◽  
Daniela Albrecht-Eckardt ◽  
Daniela Hellwig ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Candida Albicans ◽  
Transcriptional Control ◽  
Cell Damage ◽  
Iron Acquisition ◽  
Hyphal Growth ◽  
Fungal Virulence ◽  
Content Type ◽  
Human Fungal Pathogen ◽  
Full Expression

ABSTRACT The capacity of Candida albicans to reversibly change its morphology between yeast and filamentous stages is crucial for its virulence. Formation of hyphae correlates with the upregulation of genes ALS3 and ECE1, which are involved in pathogenicity processes such as invasion, iron acquisition, and host cell damage. The global repressor Tup1 and its cofactor Nrg1 are considered to be the main antagonists of hyphal development in C. albicans. However, our experiments revealed that Tup1, but not Nrg1, was required for full expression of ALS3 and ECE1. In contrast to NRG1, overexpression of TUP1 was found to inhibit neither filamentous growth nor transcription of ALS3 and ECE1. In addition, we identified the transcription factor Ahr1 as being required for full expression of both genes. A hyperactive version of Ahr1 bound directly to the promoters of ALS3 and ECE1 and induced their transcription even in the absence of environmental stimuli. This regulation worked even in the absence of the crucial hyphal growth regulators Cph1 and Efg1 but was dependent on the presence of Tup1. Overall, our results show that Ahr1 and Tup1 are key contributors in the complex regulation of virulence-associated genes in the different C. albicans morphologies. IMPORTANCE Candida albicans is a major human fungal pathogen and the leading cause of systemic Candida infections. In recent years, Als3 and Ece1 were identified as important factors for fungal virulence. Transcription of both corresponding genes is closely associated with hyphal growth. Here, we describe how Tup1, normally a global repressor of gene expression as well as of filamentation, and the transcription factor Ahr1 contribute to full expression of ALS3 and ECE1 in C. albicans hyphae. Both regulators are required for high mRNA amounts of the two genes to ensure functional relevant protein synthesis and localization. These observations identified a new aspect of regulation in the complex transcriptional control of virulence-associated genes in C. albicans.

scholarly journals A GDPase/UDPase Bifunctional Enzyme From Candida Albicans: Purification and Biochemical Characterization

2021 ◽  
Author(s):  
Jaime Alberto Bibián-García ◽  
Jorge Armando Ortiz-Ramírez ◽  
Lilia Maritza Almanza-Villegas ◽  
Ma. del Carmen Cano-Canchola ◽  
Mayra Cuéllar-Cruz ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Protein Separation ◽  
Biochemical Characterization ◽  
Opportunistic Pathogen ◽  
Protein Glycosylation ◽  
Host Cells ◽  
Cell Surface Antigens ◽  
Human Fungal Pathogen ◽  
Double Function ◽  
Systemic Infections

Abstract The most frequently isolated human fungal pathogen is Candida albicans which is responsible for about 50% of all Candida infections. In healthy individuals, this organism resides as a part of the normal microbiota in equilibrium with the host. However, under certain conditions, particularly in immunocompromised patients, this opportunistic pathogen adheres to host cells causing serious systemic infections. Thus, much effort has been dedicated to the study of its physiology with emphasis on factors associated to pathogenicity. A representative analysis deals with the mechanisms of glycoprotein assembly as many cell surface antigens and other macromolecules that modulate the immune system fall within this chemical category. In this regard, studies of the terminal protein glycosylation stage which occurs in Golgi vesicles has led to the identification of nucleotidases that convert glycosyltransferase-generated dinucleotides into the corresponding mononucleotides, thus playing a double function: their activity prevent inhibition of further glycosyl transfer by the accumulation of dinucleotides and the resulting mononucleotides are exchanged by specific membrane transporters for equimolecular amounts of sugar donors from the cytosol. Here, using a simple protocol for protein separation we isolated a bifunctional nucleotidase from C. albicans active on GDP and UDP that was characterized in terms of its molecular mass, response to bivalent ions and other factors, substrate specificity and affinity. Results are discussed in terms of the similarities and differences of this nucleotidase with similar counterparts from other organisms thus contributing to the knowledge of a bifunctional diphosphatase not described before in C. albicans.

Sign in / Sign up

Export Citation Format

Share Document