scholarly journals Roles of Candida albicans Sfl1 in Hyphal Development

2007 ◽  
Vol 6 (11) ◽  
pp. 2112-2121 ◽  
Author(s):  
Yandong Li ◽  
Chang Su ◽  
Xuming Mao ◽  
Fang Cao ◽  
Jiangye Chen
Keyword(s):  
Candida Albicans ◽  
Growth Conditions ◽  
Filamentous Growth ◽  
Negative Regulator ◽  
Specific Gene ◽  
Environmental Cues ◽  
Dimorphic Fungi ◽  
Hyphal Development ◽  
Negative Factor ◽  
Functional Homolog

ABSTRACT The ability to switch between different morphological forms is an important feature of Candida albicans and is relevant to its pathogenesis. Many conserved positive and negative transcription factors are involved in morphogenetic regulation of the two dimorphic fungi Candida albicans and Saccharomyces cerevisiae. In S. cerevisiae, the transcriptional repressor Sfl1 and the activator Flo8 function antagonistically in invasive and filamentous growth. We have previously reported that Candida albicans Flo8 is a transcription factor essential for hyphal development and virulence in C. albicans. To determine whether a similar negative factor exists in C. albicans, we identified Candida albicans Sfl1 as a functional homolog of the S. cerevisiae sfl1 mutant. Sfl1 is a negative regulator of hyphal development in C. albicans. Deletion of C. albicans SFL1 enhanced filamentous growth and hypha-specific gene expression in several media and at several growth temperatures. Overexpression of the SFL1 led to a significant reduction of filament formation. Both deletion and overexpression of the SFL1 attenuated virulence of C. albicans in a mouse model. Deleting FLO8 in an sfl1/sfl1 mutant completely blocked hyphal development in various growth conditions examined, suggesting that C. albicans Sfl1 may act as a negative regulator of filamentous growth by antagonizing Flo8 functions. We suggest that, similar to the case for S. cerevisiae, a combination of dual control by activation and repression of Flo8 and Sfl1 may contribute to the fine regulatory network in C. albicans morphogenesis responding to different environmental cues.

scholarly journals Mss11, a Transcriptional Activator, Is Required for Hyphal Development in Candida albicans

2009 ◽  
Vol 8 (11) ◽  
pp. 1780-1791 ◽  
Author(s):  
Chang Su ◽  
Yandong Li ◽  
Yang Lu ◽  
Jiangye Chen
Keyword(s):  
Candida Albicans ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Binding Partner ◽  
Hyphal Development ◽  
Functional Homolog ◽  
Upstream Activating Sequence ◽  
Enhanced Expression ◽  
Sequence Region

ABSTRACT Candida albicans undergoes a morphological transition from yeast to hyphae in response to a variety of stimuli and growth conditions. We previously isolated a LisH domain containing transcription factor Flo8, which is essential for hyphal development in C. albicans. To search the putative binding partner of Flo8 in C. albicans, we identified C. albicans Mss11, a functional homolog of Saccharomyces cerevisiae Mss11, which also contains a LisH motif at its N terminus. C. albicans Mss11 can interact with Flo8 via the LisH motif by in vivo coimmunoprecipitation. The results of a chromatin immunoprecipitation (ChIP) assay showed that more Mss11 and Flo8 proteins bound to the upstream activating sequence region of HWP1 promoter in hyphal cells than in yeast cells, and the increased binding of each of these two proteins responding to hyphal induction was dependent on the other. Overexpression of MSS11 enhanced filamentous growth. Deletion of MSS11 caused a profound defect in hyphal development and the induction of hypha-specific genes. Our data suggest that Mss11 functions as an activator in hyphal development of C. albicans. Furthermore, overexpression of FLO8 can bypass the requirement of Mss11 in filamentous formation, whereas overexpression of MSS11 failed to promote hyphae growth in flo8 mutants. In summary, we show that the expression level of MSS11 increases during hyphal induction, and the enhanced expression of MSS11 may contribute to cooperative binding of Mss11 and Flo8 to the HWP1 promoter.

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.

Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene

1999 ◽  
Vol 34 (4) ◽  
pp. 651-662 ◽  
Author(s):  
Douglas H. Brown Jr ◽  
Angela D. Giusani ◽  
Xi Chen ◽  
Carol A. Kumamoto
Keyword(s):  
Candida Albicans ◽  
Filamentous Growth ◽  
Environmental Cues

scholarly journals The zinc cluster transcription factor Rha1 is a positive filamentation regulator in Candida albicans

Genetics ◽  
2021 ◽  
Author(s):  
Raha Parvizi Omran ◽  
Bernardo Ramírez-Zavala ◽  
Walters Aji Tebung ◽  
Shuangyan Yao ◽  
Jinrong Feng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Systemic Infection ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Hyphal Development ◽  
Zinc Cluster ◽  
Function Blocks ◽  
External Signals

Abstract Zinc cluster transcription factors are essential fungal regulators of gene expression. In the pathogen Candida albicans, the gene orf19.1604 encodes a zinc cluster transcription factor regulating filament development. Hyperactivation of orf19.1604, which we have named RHA1 for Regulator of Hyphal Activity, generates wrinkled colony morphology under non-hyphal growth conditions, triggers filament formation, invasiveness, and enhanced biofilm formation and causes reduced virulence in the mouse model of systemic infection. The strain expressing activated Rha1 shows up-regulation of genes required for filamentation and cell-wall-adhesion-related proteins. Increased expression is also seen for the hyphal-inducing transcription factors Brg1 and Ume6, while the hyphal repressor Nrg1 is downregulated. Inactivation of RHA1 reduces filamentation under a variety of filament-inducing conditions. In contrast to the partial effect of either single mutant, the double rha1 ume6 mutant strain is highly defective in both serum- and Spider-medium-stimulated hyphal development. While the loss of Brg1 function blocks serum-stimulated hyphal development, this block can be significantly bypassed by Rha1 hyperactivity, and the combination of Rha1 hyperactivity and serum addition can generate significant polarization even in brg1 ume6 double mutants. Thus, in response to external signals, Rha1 functions with other morphogenesis regulators including Brg1 and Ume6, to mediate filamentation.

scholarly journals Defective Hyphal Development and Avirulence Caused by a Deletion of the SSK1 Response Regulator Gene in Candida albicans

2000 ◽  
Vol 68 (2) ◽  
pp. 518-525 ◽  
Author(s):  
José Antonio Calera ◽  
Xiao-Jiong Zhao ◽  
Richard Calderone
Keyword(s):  
Candida Albicans ◽  
Nitrogen Availability ◽  
Response Regulator ◽  
Hyphal Development ◽  
Isolation And Characterization ◽  
Solid Media ◽  
Functional Homolog ◽  
Good Target ◽  
Two Component ◽  
Hyphal Formation

ABSTRACT In a previous study, we reported the isolation and characterization of the two-component response regulator SSK1 gene ofCandida albicans. This gene is a structural but not a functional homolog of the SSK1 andmcs4 + genes of Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. In the present study, we have constructed and phenotypically characterized Δssk1 mutants of C. albicans. The results confirmed our previous observation thatCaSSK1, unlike SSK1 ormcs4 +, does not regulate cellular responses to either osmotic or oxidative stress. Instead, Δssk1 null strains showed severely reduced hyphal formation on serum agar and were totally defective in hyphal development on other solid media, such as medium 199 (pH 7.5) and Spider medium. In contrast, under conditions of low nitrogen availability on solid media, Δssk1 null strains dramatically hyperinvaded the agar. However, while forming germ tubes and hyphae in liquid media similar to those of the wild type, Δssk1 null strains flocculated in a manner similar to that of Δchk1 two-component histidine kinase mutants, which we have previously described. Finally, virulence studies indicated that SSK1 is essential for the pathogenesis ofC. albicans, suggesting that the Ssk1p response regulator could be a good target for antifungal therapy.

scholarly journals HWP1 Functions in the Morphological Development of Candida albicans Downstream ofEFG1, TUP1, and RBF1

1999 ◽  
Vol 181 (17) ◽  
pp. 5273-5279 ◽  
Author(s):  
Laura L. Sharkey ◽  
Mark D. McNemar ◽  
Susan M. Saporito-Irwin ◽  
Paul S. Sypherd ◽  
William A. Fonzi
Keyword(s):  
Candida Albicans ◽  
Target Genes ◽  
Surface Protein ◽  
Morphological Plasticity ◽  
Specific Gene ◽  
Morphological Development ◽  
Developmentally Regulated ◽  
Hyphal Development ◽  
Positive Regulators ◽  
A Cell

ABSTRACT The morphological plasticity of Candida albicans is an important determinant of pathogenicity, and nonfilamentous mutants are avirulent. HWP1, a hypha-specific gene, was identified in a genetic screen for developmentally regulated genes and encodes a cell surface protein of unknown function. Heterozygous and homozygous deletions of HWP1 resulted in a medium-conditional defect in hyphal development. HWP1 expression was blocked in a Δefg1 mutant, reduced in an Δrbf1 mutant, and derepressed in a Δtup1 mutant. Therefore,HWP1 functions downstream of the developmental regulatorsEFG1, TUP1, and RBF1. Mutation ofCPH1 had no effect on HWP1 expression, suggesting that the positive regulators of hyphal development,CPH1 and EFG1, are components of separate pathways with different target genes. The expression of a second developmentally regulated gene, ECE1, was similarly regulated by EFG1. Since ECE1 is not required for hyphal development, the regulatory role of EFG1apparently extends beyond the control of cell shape determinants. However, expression of ECE1 was not influenced byTUP1, suggesting that there may be some specificity in the regulation of morphogenic elements during hyphal development.

scholarly journals Dot6 is a major regulator of cell size and a transcriptional activator of ribosome biogenesis in the opportunistic yeast Candida albicans

2018 ◽  
Author(s):  
Julien Chaillot ◽  
Jaideep Malick ◽  
Adnane Sellam
Keyword(s):  
Candida Albicans ◽  
Cell Size ◽  
Ribosome Biogenesis ◽  
Size Control ◽  
Transcriptional Activator ◽  
Growth Conditions ◽  
Mitotic Division ◽  
Negative Regulator ◽  
Restriction Point ◽  
Tor Pathway

AbstractIn most species, size homeostasis appears to be exerted in late G1 phase as cells commit to division, called Start in yeast and the Restriction Point in metazoans. This size threshold couples cell growth to division and thereby establishes long-term size homeostasis. Our former investigations have shown that hundreds of genes markedly altered cell size under homeostatic growth conditions in the opportunistic yeast Candida albicans, but surprisingly only few of these overlapped with size control genes in the budding yeast Saccharomyces cerevisiae. Here, we investigated one of the divergent potent size regulators in C. albicans, the Myb-like HTH transcription factor Dot6. Our data demonstrated that Dot6 is a negative regulator of Start and also acts as a transcriptional activator of ribosome biogenesis (Ribi) genes. Genetic epistasis uncovered that Dot6 interacted with the master transcriptional regulator of the G1 machinery, SBF complex, but not with the Ribi and cell size regulators Sch9, Sfp1 and p38/Hog1. Dot6 was required for carbon-source modulation of cell size and it is regulated at the level of nuclear localization by TOR pathway. Our findings support a model where Dot6 acts as a hub that integrate directly growth cues via the TOR pathway to control the commitment to mitotic division at G1.

scholarly journals The zinc cluster transcription factor Rha1 is a positive filamentation regulator in Candida albicans

2020 ◽  
Author(s):  
Raha Parvizi Omran ◽  
Chris Law ◽  
Vanessa Dumeaux ◽  
Joachim Morschhäuser ◽  
Malcolm Whiteway
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Transcriptional Profiling ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Hyphal Development ◽  
Zinc Cluster ◽  
Genes Encoding

AbstractZinc cluster transcription factors are essential fungal specific regulators of gene expression. In the dimorphic pathogen Candida albicans, they control processes ranging from metabolism and stress adaptation to mating, virulence, and antifungal resistance. Here, we have identified the gene CaORF19.1604 as encoding a zinc cluster transcription factor that acts as a regulator of filament development. Hyperactivation of CaORF19.1604, which we have named RHA1 for Regulator of Hyphal Activity, leads to a wrinkled colony morphology under non-hyphal growth conditions, to pseudohyphal growth and filament formation, to invasiveness and enhanced biofilm formation.  Cells with activated Rha1 are sensitive to cell wall modifying agents such as Congo red and the echinocandin drug caspofungin but show normal sensitivity to fluconazole. RNA-sequencing-based transcriptional profiling of the activated Rha1 strain reveals the up-regulation of genes for core filamentation and cell-wall-adhesion-related proteins such as Als1, Als3, Ece1, and Hwp1. Upregulation is also seen for the genes for the hyphal-inducing transcription factors Brg1 and Ume6 and genes encoding several enzymes involved in arginine metabolism, while downregulation is seen for the hyphal repressor Nrg1. The deletion of BRG1 blocks the filamentation caused by activated Rha1, while null mutants of UME6 result in a partial block. Deletion of RHA1 can partially reduce healthy hyphal development triggered by environmental conditions such as Spider medium or serum at 37°C.In contrast to the limited effect of either single mutant, the double rha1 ume6 deletion strain is totally defective in both serum and Spider medium stimulated hyphal development. While the loss of Brg1 function blocks serum-stimulated hyphal development, this block can be significantly bypassed by Rha1 hyperactivity, and the combination of Rha1 hyperactivity and serum addition can generate significant polarization in even brg1 ume6 double mutants. Our results thus suggest that in response to external signals, Rha1 functions to facilitate the switch from an Nrg1 controlled yeast state to a Brg1/Ume6 regulated hyphal state.Author SummaryCandida albicans is the predominant human fungal pathogen, generating a mortality rate of 40% in systemically infected patients. The ability of Candida albicans to change its morphology is a determinant of its tissue penetration and invasion in response to variant host-related stimuli. The regulatory mechanism for filamentation includes a complex network of transcription factors that play roles in regulating hyphae associated genes. We identify here a new regulator of filamentation from the zinc cluster transcription factor family. We present evidence suggesting that this transcription factor assists the Nrg1/Brg1 switch regulating hyphal development.

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