scholarly journals Candida albicans Ubiquitin and Heat Shock Factor-Type Transcriptional Factors Are Involved in 2-Dodecenoic Acid-Mediated Inhibition of Hyphal Growth

2020 ◽  
Vol 8 (1) ◽  
pp. 75
Author(s):  
Dongliang Yang ◽  
Yanling Hu ◽  
Zixin Yin ◽  
Qianru Gao ◽  
Yuqian Zhang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Hyphal Growth ◽  
Filamentous Growth ◽  
Burkholderia Cenocepacia ◽  
Hyphal Morphogenesis ◽  
Expression Of Genes ◽  
Exogenous Addition ◽  
Diffusible Signal Factor ◽  
Factor Type ◽  
Hyphal Formation

Cis-2-dodecenoic acid (i.e., Burkholderia cenocepacia Diffusible Signal Factor, BDSF), a signaling molecule produced by Burkholderia cenocepacia but not by Candida albicans, can prevent Candida albicans hyphal formation. The mechanism by which BDSF controls the morphological switch of C. albicans is still unknown. To address this issue, we used the cDNA microarray method to investigate the differential expression of genes in C. albicans in the presence and absence of BDSF. The microarray result indicated that 305 genes were significantly different in the expression level. This included the downregulation of 75 genes and the upregulation of 230 genes. Based on the microarray data, a mutant library was screened to search for genes, once mutated, conferred insensitivity to BDSF. The results showed that the repressors (Ubi4 and Sfl1 proteins) and the activator (Sfl2 protein) of filamentous growth are involved in the BDSF regulation of hyphal morphogenesis. Ubi4, an ubiquitin polypeptide that participates in ubiquitin-mediated protein turnover, is the protein required for the degradation of Sfl2. Sfl1 and Sfl2 proteins antagonistically control C. albicans morphogenesis. In the hyphal induction condition, the amount of Ubi4 and Sfl1 protein increased rapidly with the exogenous addition of BDSF. As a result, the protein level of the activator of filamentous growth, Sfl2, decreased correspondingly, thereby facilitating the C. albicans cells to remain in the yeast form.

scholarly journals Release from Quorum-Sensing Molecules Triggers Hyphal Formation during Candida albicans Resumption of Growth

2005 ◽  
Vol 4 (7) ◽  
pp. 1203-1210 ◽  
Author(s):  
Brice Enjalbert ◽  
Malcolm Whiteway
Keyword(s):  
Candida Albicans ◽  
Quorum Sensing ◽  
Culture Medium ◽  
Pathogenic Fungus ◽  
Hyphal Growth ◽  
Growth Environment ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Hyphal Formation ◽  
Cyclin Genes

ABSTRACT Candida albicans is a pathogenic fungus able to change morphology in response to variations in its growth environment. Simple inoculation of stationary cells into fresh medium at 37°C, without any other manipulations, appears to be a powerful but transient inducer of hyphal formation; this process also plays a significant role in classical serum induction of hyphal formation. The mechanism appears to involve the release of hyphal repression caused by quorum-sensing molecules in the growth medium of stationary-phase cells, and farnesol has a strong but incomplete role in this process. We used DNA microarray technology to study both the resumption of growth of Candida albicans cells and molecular regulation involving farnesol. Maintaining farnesol in the culture medium during the resumption of growth both delays and reduces the induction of hypha-related genes yet triggers expression of genes encoding drug efflux components. The persistence of farnesol also prevents the repression of histone genes during hyphal growth and affects the expression of putative or demonstrated morphogenesis-regulating cyclin genes, such as HGC1, CLN3, and PCL2. The results suggest a model explaining the triggering of hyphae in the host based on quorum-sensing molecules.

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 Role for Endosomal and Vacuolar GTPases in Candida albicans Pathogenesis

2009 ◽  
Vol 77 (6) ◽  
pp. 2343-2355 ◽  
Author(s):  
Douglas A. Johnston ◽  
Karen E. Eberle ◽  
Joy E. Sturtevant ◽  
Glen E. Palmer
Keyword(s):  
Candida Albicans ◽  
Stress Resistance ◽  
Double Mutant ◽  
Hyphal Growth ◽  
Filamentous Growth ◽  
Rab Gtpases ◽  
Fungal Cell ◽  
Cellular Stresses ◽  
Vacuole Biogenesis

ABSTRACT The vacuole has crucial roles in stress resistance and adaptation of the fungal cell. Furthermore, in Candida albicans it has been observed to undergo dramatic expansion during the initiation of hyphal growth, to produce highly “vacuolated” subapical compartments. We hypothesized that these functions may be crucial for survival within the host and tissue-invasive hyphal growth. We also considered the role of the late endosome or prevacuole compartment (PVC), a distinct organelle involved in vacuolar and endocytic trafficking. We identified two Rab GTPases, encoded by VPS21 and YPT72, required for trafficking through the PVC and vacuole biogenesis, respectively. Deletion of VPS21 or YPT72 led to mild sensitivities to some cellular stresses. However, deletion of both genes resulted in a synthetic phenotype with severe sensitivity to cellular stress and impaired growth. Both the vps21Δ and ypt72Δ mutants had defects in filamentous growth, while the double mutant was completely deficient in polarized growth. The defects in hyphal growth were not suppressed by an “active” RIM101 allele or loss of the hyphal repressor encoded by TUP1. In addition, both single mutants had significant attenuation in a mouse model of hematogenously disseminated candidiasis, while the double mutant was rapidly cleared. Histological examination confirmed that the vps21Δ and ypt72Δ mutants are deficient in hyphal growth in vivo. We suggest that the PVC and vacuole are required on two levels during C. albicans infection: (i) stress resistance functions required for survival within tissue and (ii) a role in filamentous growth which may aid host tissue invasion.

scholarly journals Rac1 and Cdc42 Have Different Roles in Candida albicans Development

2006 ◽  
Vol 5 (2) ◽  
pp. 321-329 ◽  
Author(s):  
Martine Bassilana ◽  
Robert A. Arkowitz
Keyword(s):  
Candida Albicans ◽  
Plasma Membrane ◽  
G Protein ◽  
Fluorescence Recovery After Photobleaching ◽  
Hyphal Growth ◽  
Opportunistic Pathogen ◽  
Filamentous Growth ◽  
Fluorescence Recovery

ABSTRACT We investigated the role of the highly conserved G protein Rac1 in the opportunistic pathogen Candida albicans. We identified and disrupted RAC1 and show here that, in contrast to CDC42, it is not necessary for viability or serum-induced hyphal growth but is essential for filamentous growth when cells are embedded in a matrix. Rac1 is localized to the plasma membrane, yet its distribution is more homogenous than that of Cdc42, with no enrichment at the tips of either buds or hyphae. In addition, fluorescence recovery after photobleaching results indicate that Rac1 and Cdc42 have different dynamics at the membrane. Furthermore, overexpression of Rac1 does not complement Cdc42 function, and conversely, overexpression of Cdc42 does not complement Rac1 function. Thus, Rac1 and Cdc42, although highly similar to one another, have different roles in C. albicans development.

scholarly journals Sep7 Is Essential to Modify Septin Ring Dynamics and Inhibit Cell Separation during Candida albicans Hyphal Growth

2008 ◽  
Vol 19 (4) ◽  
pp. 1509-1518 ◽  
Author(s):  
Alberto González-Novo ◽  
Jaime Correa-Bordes ◽  
Leticia Labrador ◽  
Miguel Sánchez ◽  
Carlos R. Vázquez de Aldana ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Separation ◽  
Hyphal Growth ◽  
Yeast Cells ◽  
Septin Ring ◽  
Protein Levels ◽  
Hyphal Morphogenesis ◽  
Hypha Formation ◽  
Ring Dynamics ◽  
Cytoskeleton Dynamics

When Candida albicans yeast cells receive the appropriate stimulus, they switch to hyphal growth, characterized by continuous apical elongation and the inhibition of cell separation. The molecular basis of this inhibition is poorly known, despite its crucial importance for hyphal development. In C. albicans, septins are important for hypha formation and virulence. Here, we used fluorescence recovery after photobleaching analysis to characterize the dynamics of septin rings during yeast and hyphal growth. On hyphal induction, septin rings are converted to a hyphal-specific state, characterized by the presence of a frozen core formed by Sep7/Shs1, Cdc3 and Cdc12, whereas Cdc10 is highly dynamic and oscillates between the ring and the cytoplasm. Conversion of septin rings to the hyphal-specific state inhibits the translocation of Cdc14 phosphatase, which controls cell separation, to the hyphal septum. Modification of septin ring dynamics during hyphal growth is dependent on Sep7 and the hyphal-specific cyclin Hgc1, which partially controls Sep7 phosphorylation status and protein levels. Our results reveal a link between the cell cycle machinery and septin cytoskeleton dynamics, which inhibits cell separation in the filaments and is essential for hyphal morphogenesis.

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 The Candida albicans ATO Gene Family Promotes Neutralization of the Macrophage Phagolysosome

2015 ◽  
Vol 83 (11) ◽  
pp. 4416-4426 ◽  
Author(s):  
Heather A. Danhof ◽  
Michael C. Lorenz
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Hyphal Growth ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Ph Change ◽  
Content Type ◽  
Ammonia Release ◽  
Hyphal Formation

ABSTRACTCandida albicansis an opportunistic human fungal pathogen that causes a variety of diseases, ranging from superficial mucosal to life-threatening systemic infections, the latter particularly in patients with defects in innate immune function.C. albicanscells phagocytosed by macrophages undergo a dramatic change in their metabolism in which amino acids are a key nutrient. We have shown that amino acid catabolism allows the cell to neutralize the phagolysosome and initiate hyphal growth. We show here that members of the 10-geneATOfamily, which are induced by phagocytosis or the presence of amino acids in an Stp2-dependent manner and encode putative acetate or ammonia transporters, are important effectors of this pH changein vitroand in macrophages. When grown with amino acids as the sole carbon source, the deletion ofATO5or the expression of a dominant-negativeATO1G53Dallele results in a delay in alkalinization, a defect in hyphal formation, and a reduction in the amount of ammonia released from the cell. These strains also form fewer hyphae after phagocytosis, have a reduced ability to escape macrophages, and reside in more acidic phagolysosomal compartments than wild-type cells. Furthermore, overexpression of many of the 10ATOgenes accelerates ammonia release, and anato5Δ ATO1G53Ddouble mutant strain has additive alkalinization and ammonia release defects. Taken together, these results indicate that the Ato protein family is a key mediator of the metabolic changes that allowC. albicansto overcome the macrophage innate immunity barrier.

scholarly journals Functional Characterization of Myosin I Tail Regions in Candida albicans

2004 ◽  
Vol 3 (5) ◽  
pp. 1272-1286 ◽  
Author(s):  
Ursula Oberholzer ◽  
Tatiana L. Iouk ◽  
David Y. Thomas ◽  
Malcolm Whiteway
Keyword(s):  
Candida Albicans ◽  
Functional Characterization ◽  
Hyphal Growth ◽  
Tail Domain ◽  
Cortical Actin ◽  
Pathogenic Yeast ◽  
Rhodamine Phalloidin ◽  
Myosin I ◽  
Hyphal Formation ◽  
Hyphal Tip

ABSTRACT The molecular motor myosin I is required for hyphal growth in the pathogenic yeast Candida albicans. Specific myosin I functions were investigated by a deletion analysis of five neck and tail regions. Hyphal formation requires both the TH1 region and the IQ motifs. The TH2 region is important for optimal hyphal growth. All of the regions, except for the SH3 and acidic (A) regions that were examined individually, were required for the localization of myosin I at the hyphal tip. Similarly, all of the domains were required for the association of myosin I with pelletable actin-bound complexes. Moreover, the hyphal tip localization of cortical actin patches, identified by both rhodamine-phalloidin staining and Arp3-green fluorescent protein signals, was dependent on myosin I. Double deletion of the A and SH3 domains depolarized the distribution of the cortical actin patches without affecting the ability of the mutant to form hyphae, suggesting that myosin I has distinct functions in these processes. Among the six myosin I tail domain mutants, the ability to form hyphae was strictly correlated with endocytosis. We propose that the uptake of cell wall remodeling enzymes and excess plasma membrane is critical for hyphal formation.

scholarly journals A Candida albicans Temperature-Sensitivecdc12-6Mutant Identifies Roles for Septins in Selection of Sites of Germ Tube Formation and Hyphal Morphogenesis

2012 ◽  
Vol 11 (10) ◽  
pp. 1210-1218 ◽  
Author(s):  
Lifang Li ◽  
Chengda Zhang ◽  
James B. Konopka
Keyword(s):  
Candida Albicans ◽  
Germ Tube ◽  
Leading Edge ◽  
Hyphal Growth ◽  
Striking Difference ◽  
Temperature Sensitive ◽  
Content Type ◽  
Hyphal Morphogenesis ◽  
Germ Tubes ◽  
Selection Of

ABSTRACTSeptins were identified for their role in septation inSaccharomyces cerevisiaeand were subsequently implicated in other morphogenic processes. To study septins inCandida albicanshyphal morphogenesis, a temperature-sensitive mutation was created that altered the C terminus of the essential Cdc12 septin. Thecdc12-6cells grew well at room temperature, but at 37°C they displayed expected defects in septation, nuclear localization, and bud morphogenesis. Although serum stimulated thecdc12-6cells at 37°C to form germ tube outgrowths, the mutant could not maintain polarized hyphal growth and instead formed chains of elongated cell compartments. Serum also stimulated thecdc12-6mutant to induce a hyphal reporter gene (HWP1-GFP) and a characteristic zone of filipin staining at the leading edge of growth. Interestingly,cdc12-6cells shifted to 37°C in the absence of serum gradually displayed enriched filipin staining at the tip, which may be due to the altered cell cycle regulation. A striking difference from the wild type was that thecdc12-6cells frequently formed a second germ tube in close proximity to the first. The mutant cells also failed to form the diffuse band of septins at the base of germ tubes and hyphae, indicating that this septin band plays a role in preventing proximal formation of germ tubes in a manner analogous to bud site selection. These studies demonstrate that not only are septins important for cytokinesis, but they also promote polarized morphogenesis and selection of germ tube sites that may help disseminate an infection in host tissues.

scholarly journals A conserved regulator controls asexual sporulation in the fungal pathogen Candida albicans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Arturo Hernández-Cervantes ◽  
Sadri Znaidi ◽  
Lasse van Wijlick ◽  
Iryna Denega ◽  
Virginia Basso ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Chromatin Immunoprecipitation ◽  
Fungal Pathogen ◽  
Hyphal Growth ◽  
Second Phase ◽  
Asexual Sporulation ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Genome Wide Expression

AbstractTranscription factor Rme1 is conserved among ascomycetes and regulates meiosis and pseudohyphal growth in Saccharomyces cerevisiae. The genome of the meiosis-defective pathogen Candida albicans encodes an Rme1 homolog that is part of a transcriptional circuitry controlling hyphal growth. Here, we use chromatin immunoprecipitation and genome-wide expression analyses to study a possible role of Rme1 in C. albicans morphogenesis. We find that Rme1 binds upstream and activates the expression of genes that are upregulated during chlamydosporulation, an asexual process leading to formation of large, spherical, thick-walled cells during nutrient starvation. RME1 deletion abolishes chlamydosporulation in three Candida species, whereas its overexpression bypasses the requirement for chlamydosporulation cues and regulators. RME1 expression levels correlate with chlamydosporulation efficiency across clinical isolates. Interestingly, RME1 displays a biphasic pattern of expression, with a first phase independent of Rme1 function and dependent on chlamydospore-inducing cues, and a second phase dependent on Rme1 function and independent of chlamydospore-inducing cues. Our results indicate that Rme1 plays a central role in chlamydospore development in Candida species.

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