scholarly journals Role for the SCFCDC4Ubiquitin Ligase inCandida albicansMorphogenesis

2005 ◽  
Vol 16 (6) ◽  
pp. 2772-2785 ◽  
Author(s):  
Avigail Atir-Lande ◽  
Tsvia Gildor ◽  
Daniel Kornitzer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Ubiquitin Ligase ◽  
Fungal Pathogen ◽  
Ectopic Expression ◽  
Hyphal Growth ◽  
Yeast Form ◽  
Epistasis Analysis ◽  
F Box Protein

The ability of Candida albicans, a major fungal pathogen, to switch between a yeast form, and a hyphal (mold) form is recognized as being important for the ability of the organism to invade the host and cause disease. We found that a C. albicans mutant deleted for CaCDC4, a homologue of the Saccharomyces cerevisiae F-box protein component of the SCFCDC4ubiquitin ligase, is viable and displays constitutive filamentous, mostly hyphal, growth. The phenotype of the Cacdc4–/– mutant suggests that ubiquitin-mediated protein degradation is involved in the regulation of the dimorphic switch of C. albicans and that one or more regulators of the yeast-to-mold switch are among the substrates of SCFCaCDC4. Epistasis analysis indicates that the Cacdc4–/– phenotype is largely independent of the filamentation-inducing transcription factors Efg1 and Cph1. We identify C. albicans Far1 and Sol1, homologues of the S. cerevisiae SCFCDC4substrates Far1 and Sic1, and show that Sol1 is a substrate of C. albicans Cdc4. Neither protein is essential for the hyphal phenotype of the Cacdc4–/– mutant. However, ectopic expression and deletion of SOL1 indicate a role for this gene in C. albicans morphogenesis.

scholarly journals Cdc24, the GDP-GTP Exchange Factor for Cdc42, Is Required for Invasive Hyphal Growth of Candida albicans

2003 ◽  
Vol 2 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Martine Bassilana ◽  
James Blyth ◽  
Robert A. Arkowitz
Keyword(s):  
Candida Albicans ◽  
Protein Kinase ◽  
G Protein ◽  
Fungal Pathogen ◽  
Ectopic Expression ◽  
Hyphal Growth ◽  
Mitogen Activated Protein Kinase ◽  
Filamentous Form ◽  
Exchange Factor ◽  
Polarity Establishment

ABSTRACT Candida albicans, the most common human fungal pathogen, is particularly problematic for immunocompromised individuals. The reversible transition of this fungal pathogen to a filamentous form that invades host tissue is important for its virulence. Although different signaling pathways such as a mitogen-activated protein kinase and a protein kinase A cascade are critical for this morphological transition, the function of polarity establishment proteins in this process has not been determined. We examined the role of four different polarity establishment proteins in C. albicans invasive growth and virulence by using strains in which one copy of each gene was deleted and the other copy expressed behind the regulatable promoter MET3. Strikingly, mutants with ectopic expression of either the Rho G-protein Cdc42 or its exchange factor Cdc24 are unable to form invasive hyphal filaments and germ tubes in response to serum or elevated temperature and yet grow normally as a budding yeast. Furthermore, these mutants are avirulent in a mouse model for systemic infection. This function of the Cdc42 GTPase module is not simply a general feature of polarity establishment proteins. Mutants with ectopic expression of the SH3 domain containing protein Bem1 or the Ras-like G-protein Bud1 can grow in an invasive fashion and are virulent in mice, albeit with reduced efficiency. These results indicate that a specific regulation of Cdc24/Cdc42 activity is required for invasive hyphal growth and suggest that these proteins are required for pathogenicity of C. albicans.

scholarly journals High Resistance to Oxidative Stress in the Fungal Pathogen Candida glabrata Is Mediated by a Single Catalase, Cta1p, and Is Controlled by the Transcription Factors Yap1p, Skn7p, Msn2p, and Msn4p

2008 ◽  
Vol 7 (5) ◽  
pp. 814-825 ◽  
Author(s):  
Mayra Cuéllar-Cruz ◽  
Marcela Briones-Martin-del-Campo ◽  
Israel Cañas-Villamar ◽  
Javier Montalvo-Arredondo ◽  
Lina Riego-Ruiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Adaptive Response ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Systemic Infection ◽  
Oxidative Stress Response

ABSTRACT We characterized the oxidative stress response of Candida glabrata to better understand the virulence of this fungal pathogen. C. glabrata could withstand higher concentrations of H2O2 than Saccharomyces cerevisiae and even Candida albicans. Stationary-phase cells were extremely resistant to oxidative stress, and this resistance was dependent on the concerted roles of stress-related transcription factors Yap1p, Skn7p, and Msn4p. We showed that growing cells of C. glabrata were able to adapt to high levels of H2O2 and that this adaptive response was dependent on Yap1p and Skn7p and partially on the general stress transcription factors Msn2p and Msn4p. C. glabrata has a single catalase gene, CTA1, which was absolutely required for resistance to H2O2 in vitro. However, in a mouse model of systemic infection, a strain lacking CTA1 showed no effect on virulence.

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 Transcriptional control of hypoxic hyphal growth in the fungal pathogen Candida albicans

2021 ◽  
Author(s):  
Henry Manon ◽  
Anais Burgain ◽  
Faiza Tebbji ◽  
Adnane Sellam
Keyword(s):  
Candida Albicans ◽  
Transcription Factors ◽  
Fungal Pathogen ◽  
Transcriptional Control ◽  
Genetic Interaction ◽  
Transcriptional Profiling ◽  
Hyphal Growth ◽  
Negative Regulator ◽  
Functional Relationships ◽  
Chip Chip

Background: The ability of Candida albicans, an important human fungal pathogen, to develop filamentous forms is a crucial determinant for host invasion and virulence. Filamentation is triggered by different host environmental cues such as temperature and pH. Hypoxia, the dominant conditions that C. albicans encounters inside the human host, promote filamentation, however, the contributing mechanisms remain poorly characterized. Methods: We performed a quantitative analysis of gene deletion mutants from different collections of protein kinases and transcriptional regulators in C. albicans to identify specific modulators of the hypoxic filamentation. We used genome-wide transcriptional profiling (Microarrays) and promoter occupancy (ChIP-chip) to characterize regulons of two transcription factors that were associated with the hypoxic filamentation. Genetic interactions were also used to assess functional relationships among the newly identified modulators of hypoxic filamentation and the well-known C. albicans core morphogenetic regulators. Results: Our genetic screen uncovered two transcription factors, Ahr1 and Tye7, that act as prominent regulators of C. albicans filamentation specifically under hypoxia. Both ahr1 and tye7 mutants exhibited a hyperfilamentous phenotype specifically under an oxygen-depleted environment suggesting that these transcription factors act as a negative regulator of hypoxic filamentation. By combining microarray and ChIP-chip data, we have characterized the set of genes that are directly modulated by Ahr1 and Tye7. We found that both Ahr1 and Tye7 modulate a different set of genes and biological processes. Our genetic epistasis analysis supports our genomic finding and suggests that Ahr1 and Tye7 act independently to modulate hyphal growth in response to hypoxia. Furthermore, our genetic interaction experiments uncovered that Ahr1 and Tye7 repress the hypoxic filamentation growth via the Efg1 and Ras1/Cyr1 pathways, respectively. Conclusion: In sum, this investigation represents an informative resource toward the understanding of how hypoxia, the predominant condition inside the host, shapes the invasive filamentous growth of C. albicans.

scholarly journals Candida albicans INT1-Induced Filamentation in Saccharomyces cerevisiae Depends on Sla2p

2001 ◽  
Vol 21 (4) ◽  
pp. 1272-1284 ◽  
Author(s):  
Catherine M. Asleson ◽  
Eric S. Bensen ◽  
Cheryl A. Gale ◽  
A.-S. Melms ◽  
Cornelia Kurischko ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Hyphal Growth ◽  
Filamentous Growth ◽  
Small Subset ◽  
Polarized Growth ◽  
Epistasis Analysis ◽  
Hyphal Morphogenesis ◽  
C Terminus ◽  
Important Virulence Factor

ABSTRACT The Candida albicans INT1 gene is important for hyphal morphogenesis, adherence, and virulence (C. Gale, C. Bendel, M. McClellan, M. Hauser, J. M. Becker, J. Berman, and M. Hostetter, Science 279:1355–1358, 1998). The ability to switch between yeast and hyphal morphologies is an important virulence factor in this fungal pathogen. When INT1 is expressed in Saccharomyces cerevisiae, cells grow with a filamentous morphology that we exploited to gain insights into how C. albicans regulates hyphal growth. In S. cerevisiae, INT1-induced filamentous growth was affected by a small subset of actin mutations and a limited set of actin-interacting proteins including Sla2p, anS. cerevisiae protein with similarity in its C terminus to mouse talin. Interestingly, while SLA2 was required forINT1-induced filamentous growth, it was not required for polarized growth in response to several other conditions, suggesting that Sla2p is not required for polarized growth per se. The morphogenesis checkpoint, mediated by Swe1p, contributes toINT1-induced filamentous growth; however, epistasis analysis suggests that Sla2p and Swe1p contribute toINT1-induced filamentous growth through independent pathways. The C. albicans SLA2 homolog (CaSLA2) complements S. cerevisiae sla2Δ mutants for growth at 37°C and INT1-induced filamentous growth. Furthermore, in a C. albicans Casla2/Casla2 strain, hyphal growth did not occur in response to either nutrient deprivation or to potent stimuli, such as mammalian serum. Thus, through analysis ofINT1-induced filamentous growth in S. cerevisiae, we have identified a C. albicans gene,SLA2, that is required for hyphal growth in C. albicans.

scholarly journals Msn2- and Msn4-Like Transcription Factors Play No Obvious Roles in the Stress Responses of the Fungal Pathogen Candida albicans

2004 ◽  
Vol 3 (5) ◽  
pp. 1111-1123 ◽  
Author(s):  
Susan Nicholls ◽  
Melissa Straffon ◽  
Brice Enjalbert ◽  
André Nantel ◽  
Susan Macaskill ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Transcription Factors ◽  
Stress Responses ◽  
Ectopic Expression ◽  
Heavy Metal Stress ◽  
Luciferase Reporter ◽  
Response Element ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Adverse Environmental Conditions

ABSTRACT In Saccharomyces cerevisiae, the (C2H2)2 zinc finger transcription factors Msn2 and Msn4 play central roles in responses to a range of stresses by activating gene transcription via the stress response element (STRE; CCCCT). The pathogen Candida albicans displays stress responses that are thought to help it survive adverse environmental conditions encountered within its human host. However, these responses differ from those in S. cerevisiae, and hence we predicted that the roles of Msn2- and Msn4-like proteins might have been functionally reassigned in C. albicans. C. albicans has two such proteins: CaMsn4 and Mnl1 (for Msn2- and Msn4-like). CaMSN4, but not MNL1, weakly complemented the inability of an S. cerevisiae msn2 msn4 mutant to activate a STRE-lacZ reporter. Also, the disruption of CaMsn4 and Mnl1 had no discernible effect upon the resistance of C. albicans to heat, osmotic, ethanol, nutrient, oxidative, or heavy-metal stress or upon the stress-activated transcriptome in C. albicans. Furthermore, although Cap1-dependent activation of a Yap response element-luciferase reporter was observed, a STRE reporter was not activated in response to stresses in C. albicans. Ectopic expression of CaMsn4 or Mnl1 did not affect the cellular or molecular responses of C. albicans to stress. Under the conditions tested, the putative activation and DNA binding domains of CaMsn4 did not appear to be functional. These data suggest that CaMsn4 and Mnl1 do not contribute significantly to stress responses in C. albicans. The data are consistent with the idea that stress signaling in this fungus has diverged significantly from that in budding yeast.

scholarly journals Cell Wall-Related Bionumbers and Bioestimates of Saccharomyces cerevisiae and Candida albicans

2013 ◽  
Vol 13 (1) ◽  
pp. 2-9 ◽  
Author(s):  
Frans M. Klis ◽  
Chris G. de Koster ◽  
Stanley Brul
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Candida Albicans ◽  
Cell Size ◽  
Pathogenic Fungus ◽  
Turgor Pressure ◽  
Hyphal Growth ◽  
Biological Research ◽  
Content Type ◽  
Starting Point

ABSTRACTBionumbers and bioestimates are valuable tools in biological research. Here we focus on cell wall-related bionumbers and bioestimates of the budding yeastSaccharomyces cerevisiaeand the polymorphic, pathogenic fungusCandida albicans. We discuss the linear relationship between cell size and cell ploidy, the correlation between cell size and specific growth rate, the effect of turgor pressure on cell size, and the reason why using fixed cells for measuring cellular dimensions can result in serious underestimation ofin vivovalues. We further consider the evidence that individual buds and hyphae grow linearly and that exponential growth of the population results from regular formation of new daughter cells and regular hyphal branching. Our calculations show that hyphal growth allowsC. albicansto cover much larger distances per unit of time than the yeast mode of growth and that this is accompanied by strongly increased surface expansion rates. We therefore predict that the transcript levels of genes involved in wall formation increase during hyphal growth. Interestingly, wall proteins and polysaccharides seem barely, if at all, subject to turnover and replacement. A general lesson is how strongly most bionumbers and bioestimates depend on environmental conditions and genetic background, thus reemphasizing the importance of well-defined and carefully chosen culture conditions and experimental approaches. Finally, we propose that the numbers and estimates described here offer a solid starting point for similar studies of other cell compartments and other yeast species.

scholarly journals Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of the Pathogenic Yeast Candida albicans

Antibiotics ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Untreated Control ◽  
Morphological Transition ◽  
Pathogenic Yeast ◽  
Yeast Form ◽  
Human Fungal Pathogen ◽  
Morphological Transitions ◽  
Simple Carbohydrate

The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.

scholarly journals Candida albicans Ume6, a Filament-Specific Transcriptional Regulator, Directs Hyphal Growth via a Pathway Involving Hgc1 Cyclin-Related Protein

2010 ◽  
Vol 9 (9) ◽  
pp. 1320-1328 ◽  
Author(s):  
Patricia L. Carlisle ◽  
David Kadosh
Keyword(s):  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Constitutive Expression ◽  
Transcriptional Regulator ◽  
Hyphal Growth ◽  
Related Protein ◽  
Content Type ◽  
Epistasis Analysis ◽  
Dependent Inactivation ◽  
Hyphal Formation

ABSTRACT The ability of Candida albicans, the most common human fungal pathogen, to transition from yeast to hyphae is essential for pathogenicity. While a variety of transcription factors important for filamentation have been identified and characterized, links between transcriptional regulators of C. albicans morphogenesis and molecular mechanisms that drive hyphal growth are not well defined. We have previously observed that constitutive expression of UME6, which encodes a filament-specific transcriptional regulator, is sufficient to direct hyphal growth in the absence of filament-inducing conditions. Here we show that HGC1, encoding a cyclin-related protein necessary for hyphal growth under filament-inducing conditions, is specifically important for agar invasion, hyphal extension, and formation of true septa in response to constitutive UME6 expression under non-filament-inducing conditions. HGC1-dependent inactivation of Rga2, a Cdc42 GTPase activating protein (GAP), also appears to be important for these processes. In response to filament-inducing conditions, HGC1 is induced prior to UME6 although UME6 controls the level and duration of HGC1 expression, which are likely to be important for hyphal extension. Interestingly, an epistasis analysis suggests that UME6 and HGC1 play distinct roles during early filament formation. These findings establish a link between a key regulator of filamentation and a downstream mechanism important for hyphal formation. In addition, this study demonstrates that a strain expressing constitutive high levels of UME6 provides a powerful strategy to specifically dissect downstream mechanisms important for hyphal development in the absence of complex filament-inducing conditions.

scholarly journals Defects in Assembly of the Extracellular Matrix Are Responsible for Altered Morphogenesis of a Candida albicans phr1 Mutant

1998 ◽  
Vol 180 (1) ◽  
pp. 163-166 ◽  
Author(s):  
Laura Popolo ◽  
Marina Vai
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Parental Strain ◽  
Germ Tube ◽  
Null Mutant ◽  
Yeast Form ◽  
Insoluble Glucan ◽  
Cross Linker ◽  
External Ph

ABSTRACT Analysis of Candida albicans cells using antibodies directed against Gas1p/Ggp1p, Saccharomyces cerevisiaehomolog of Phr1p, revealed that Phr1p is a glycoprotein of about 88 kDa whose accumulation increases with the rise of external pH. This polypeptide is present both in the yeast form and during germ tube induction. In the Phr1− cells at pH 8 the solubility of glucans in alkali is greatly affected. In the parental strain the alkali-soluble/-insoluble glucan ratio shows a 50% decrease at pH 8 with respect to pH 4.5, whereas in the null mutant it is unchanged, indicating the lack of a polymer cross-linker activity induced by the rise of pH. The mutant has a sixfold increase in chitin level and is hypersensitive to calcofluor. Consistently with a role of chitin in strengthening the cell wall, Phr1− cells are more sensitive to nikkomycin Z than the parental strain.

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