scholarly journals Adaptations of the Secretome of Candida albicans in Response to Host-Related Environmental Conditions

2015 ◽  
Vol 14 (12) ◽  
pp. 1165-1172 ◽  
Author(s):  
Frans M. Klis ◽  
Stanley Brul
Keyword(s):  
Candida Albicans ◽  
Cell Surface ◽  
Human Body ◽  
Environmental Conditions ◽  
Surface Stress ◽  
Hyphal Growth ◽  
Content Type ◽  
General Response ◽  
Culture Supernatants

ABSTRACTThe wall proteome and the secretome of the fungal pathogenCandida albicanshelp it to thrive in multiple niches of the human body. Mass spectrometry has allowed researchers to study the dynamics of both subproteomes. Here, we discuss some major responses of the secretome to host-related environmental conditions. Three β-1,3-glucan-modifying enzymes, Mp65, Sun41, and Tos1, are consistently found in large amounts in culture supernatants, suggesting that they are needed for construction and expansion of the cell wall β-1,3-glucan layer and thus correlate with growth and might serve as diagnostic biomarkers. The genesENG1,CHT3, andSCW11, which encode an endoglucanase, the major chitinase, and a β-1,3-glucan-modifying enzyme, respectively, are periodically expressed and peak in M/G1. The corresponding protein abundances in the medium correlate with the degree of cell separation during single-yeast-cell, pseudohyphal, and hyphal growth. We also discuss the observation that cells treated with fluconazole, or other agents causing cell surface stress, form pseudohyphal aggregates. Fluconazole-treated cells secrete abundant amounts of the transglucosylase Phr1, which is involved in the accumulation of β-1,3-glucan in biofilms, raising the question whether this is a general response to cell surface stress. Other abundant secretome proteins also contribute to biofilm formation, emphasizing the important role of secretome proteins in this mode of growth. Finally, we discuss the relevance of these observations to therapeutic intervention. Together, these data illustrate thatC. albicansactively adapts its secretome to environmental conditions, thus promoting its survival in widely divergent niches of the human body.

scholarly journals Role of Transcription Factor CaNdt80p in Cell Separation, Hyphal Growth, and Virulence in Candida albicans

2010 ◽  
Vol 9 (4) ◽  
pp. 634-644 ◽  
Author(s):  
Adnane Sellam ◽  
Christopher Askew ◽  
Elias Epp ◽  
Faiza Tebbji ◽  
Alaka Mullick ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Cell Separation ◽  
Hyphal Growth ◽  
Functional Domain ◽  
Transcription Factor Family ◽  
Content Type ◽  
Genes Encoding

ABSTRACT The NDT80/PhoG transcription factor family includes ScNdt80p, a key modulator of the progression of meiotic division in Saccharomyces cerevisiae. In Candida albicans, a member of this family, CaNdt80p, modulates azole sensitivity by controlling the expression of ergosterol biosynthesis genes. We previously demonstrated that CaNdt80p promoter targets, in addition to ERG genes, were significantly enriched in genes related to hyphal growth. Here, we report that CaNdt80p is indeed required for hyphal growth in response to different filament-inducing cues and for the proper expression of genes characterizing the filamentous transcriptional program. These include noteworthy genes encoding cell wall components, such as HWP1, ECE1, RBT4, and ALS3. We also show that CaNdt80p is essential for the completion of cell separation through the direct transcriptional regulation of genes encoding the chitinase Cht3p and the cell wall glucosidase Sun41p. Consistent with their hyphal defect, ndt80 mutants are avirulent in a mouse model of systemic candidiasis. Interestingly, based on functional-domain organization, CaNdt80p seems to be a unique regulator characterizing fungi from the CTG clade within the subphylum Saccharomycotina. Therefore, this study revealed a new role of the novel member of the fungal NDT80 transcription factor family as a regulator of cell separation, hyphal growth, and virulence.

scholarly journals Roles of the Transcription Factors Sfl2 and Efg1 in White-Opaque Switching in a/α Strains ofCandida albicans

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Yang-Nim Park ◽  
Kayla Conway ◽  
Thomas P. Conway ◽  
Karla J. Daniels ◽  
David R. Soll
Keyword(s):  
Candida Albicans ◽  
Transcription Factors ◽  
Carbon Source ◽  
Environmental Conditions ◽  
Fungal Pathogen ◽  
Type Locus ◽  
Content Type ◽  
Physiological Conditions ◽  
Ofcandida Albicans

ABSTRACTCandida albicansremains the most pervasive fungal pathogen colonizing humans. The majority of isolates from hosts are heterozygous at the mating type locus (MTLa/α), and a third of these have recently been shown to be capable of switching to the opaque phenotype. Here we have investigated the roles of two transcription factors (TFs) Sfl2 and Efg1, in repressing switching ina/α strains. Deleting either gene results in the capacity ofa/α cells to switch to opaque en masse under facilitating environmental conditions, which includeN-acetylglucosamine (GlcNAc) as the carbon source, physiological temperature (37°C), and high CO2(5%). These conditions are similar to those in the host. Our results further reveal that while glucose is a repressor ofsfl2Δ andefg1Δ switching, GlcNAc is an inducer. Finally, we show that when GlcNAc is the carbon source, and the temperature is low (25°C), theefg1Δ mutants, but not thesfl2Δ mutants, form a tiny, elongate cell, which differentiates into an opaque cell when transferred to conditions optimal fora/α switching. These results demonstrate that at least two TFs, Sfl2 and Efg1, repress switching ina/α cells and thata/α strains with either ansfl2Δ orefg1Δ mutation can switch en masse but only under physiological conditions. The role of opaquea/α cells in commensalism and pathogenesis must, therefore, be investigated.IMPORTANCEMore than 95% ofCandida albicansstrains isolated from humans areMTLa/α, and approximately a third of these can undergo the white-to-opaque transition. Therefore, besides being a requirement forMTL-homozygous strains to mate, the opaque phenotype very likely plays a role in the commensalism and pathogenesis of nonmating,a/α populations colonizing humans.

scholarly journals Farnesol and Cyclic AMP Signaling Effects on the Hypha-to-Yeast Transition in Candida albicans

2012 ◽  
Vol 11 (10) ◽  
pp. 1219-1225 ◽  
Author(s):  
Allia K. Lindsay ◽  
Aurélie Deveau ◽  
Amy E. Piispanen ◽  
Deborah A. Hogan
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Fungal Pathogen ◽  
Hyphal Growth ◽  
Morphological Plasticity ◽  
Camp Signaling ◽  
Environmental Cues ◽  
Transcriptional Repressors ◽  
Content Type

ABSTRACTCandida albicans, a fungal pathogen of humans, regulates its morphology in response to many environmental cues and this morphological plasticity contributes to virulence. Farnesol, an autoregulatory molecule produced byC. albicans, inhibits the induction of hyphal growth by inhibiting adenylate cyclase (Cyr1). The role of farnesol and Cyr1 in controlling the maintenance of hyphal growth has been less clear. Here, we demonstrate that preformed hyphae transition to growth as yeast in response to farnesol and that strains with increased cyclic AMP (cAMP) signaling exhibit more resistance to farnesol. Exogenous farnesol did not induce the hypha-to-yeast transition in mutants lacking the Tup1 or Nrg1 transcriptional repressors in embedded conditions. Although body temperature is not required for embedded hyphal growth, we found that the effect of farnesol on the hypha-to-yeast transition varies inversely with temperature. Our model of Cyr1 activity being required for filamentation is also supported by our liquid assay data, which show increased yeast formation when preformed filaments are treated with farnesol. Together, these data suggest that farnesol can modulate morphology in preformed hyphal cells and that the repression of hyphal growth maintenance likely occurs through the inhibition of cAMP signaling.

scholarly journals Global Role of Cyclic AMP Signaling in pH-Dependent Responses in Candida albicans

mSphere ◽  
2016 ◽  
Vol 1 (6) ◽  
Author(s):  
Jeffrey M. Hollomon ◽  
Nora Grahl ◽  
Sven D. Willger ◽  
Katja Koeppen ◽  
Deborah A. Hogan
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Hyphal Growth ◽  
Filamentous Growth ◽  
Low Ph ◽  
Camp Signaling ◽  
Content Type ◽  
Neutral Ph ◽  
Ph Dependent

ABSTRACT Candida albicans is a human commensal and the causative agent of candidiasis, a potentially invasive and life-threatening infection. C. albicans experiences wide changes in pH during both benign commensalism (a common condition) and pathogenesis, and its morphology changes in response to this stimulus. Neutral pH is considered an activator of hyphal growth through Rim101, but the effect of low pH on other morphology-related pathways has not been extensively studied. We sought to determine the role of cyclic AMP signaling, a central regulator of morphology, in the sensing of pH. In addition, we asked broadly what cellular processes were altered by pH in both the presence and absence of this important signal integration system. We concluded that cAMP signaling is impacted by pH and that cAMP broadly impacts C. albicans physiology in both pH-dependent and -independent ways. Candida albicans behaviors are affected by pH, an important environmental variable. Filamentous growth is a pH-responsive behavior, where alkaline conditions favor hyphal growth and acid conditions favor growth as yeast. We employed filamentous growth as a tool to study the impact of pH on the hyphal growth regulator Cyr1, and we report that downregulation of cyclic AMP (cAMP) signaling by acidic pH contributes to the inhibition of hyphal growth in minimal medium with GlcNAc. Ras1 and Cyr1 are generally required for efficient hyphal growth, and the effects of low pH on Ras1 proteolysis and GTP binding are consistent with diminished cAMP output. Active alleles of ras1 do not suppress the hyphal growth defect at low pH, while dibutyryl cAMP partially rescues filamentous growth at low pH in a cyr1 mutant. These observations are consistent with Ras1-independent downregulation of Cyr1 by low pH. We also report that extracellular pH leads to rapid and prolonged decreases in intracellular pH, and these changes may contribute to reduced cAMP signaling by reducing intracellular bicarbonate pools. Transcriptomics analyses found that the loss of Cyr1 at either acidic or neutral pH leads to increases in transcripts involved in carbohydrate catabolism and protein translation and glycosylation and decreases in transcripts involved in oxidative metabolism, fluconazole transport, metal transport, and biofilm formation. Other pathways were modulated in pH-dependent ways. Our findings indicate that cAMP has a global role in pH-dependent responses, and this effect is mediated, at least in part, through Cyr1 in a Ras1-independent fashion. IMPORTANCE Candida albicans is a human commensal and the causative agent of candidiasis, a potentially invasive and life-threatening infection. C. albicans experiences wide changes in pH during both benign commensalism (a common condition) and pathogenesis, and its morphology changes in response to this stimulus. Neutral pH is considered an activator of hyphal growth through Rim101, but the effect of low pH on other morphology-related pathways has not been extensively studied. We sought to determine the role of cyclic AMP signaling, a central regulator of morphology, in the sensing of pH. In addition, we asked broadly what cellular processes were altered by pH in both the presence and absence of this important signal integration system. We concluded that cAMP signaling is impacted by pH and that cAMP broadly impacts C. albicans physiology in both pH-dependent and -independent ways.

scholarly journals Role of Endothelial Cell Septin 7 in the Endocytosis of Candida albicans

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Quynh T. Phan ◽  
David K. Eng ◽  
Serge Mostowy ◽  
Hyunsook Park ◽  
Pascale Cossart ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Candida Albicans ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Affinity Purification ◽  
Surface Proteins ◽  
Microbial Pathogens ◽  
Actin Microfilaments ◽  
Content Type

ABSTRACTCandida albicansinvades endothelial cells by binding to N-cadherin and other cell surface receptors. This binding induces rearrangement of endothelial cell actin microfilaments, which results in the formation of pseudopods that surround the organism and pull it into the endothelial cell. Here, we investigated the role of endothelial cell septin 7 (SEPT7) in the endocytosis ofC. albicanshyphae. Using confocal microscopy, we determined that SEPT7 accumulated with N-cadherin and actin microfilaments aroundC. albicansas it was endocytosed by endothelial cells. Affinity purification studies indicated that a complex containing N-cadherin and SEPT7 was recruited byC. albicansand that formation of this complex aroundC. albicanswas mediated by the fungal Als3 and Ssa1 invasins. Knockdown of N-cadherin by small interfering RNA (siRNA) reduced recruitment of SEPT7 toC. albicans, suggesting that N-cadherin functions as a link between SEPT7 and the fungus. Also, depolymerization of actin microfilaments with cytochalasin D decreased the association between SEPT7 and N-cadherin and inhibited recruitment of both SEPT7 and N-cadherin toC. albicans, indicating the necessity of an intact cytoskeleton in the functional interaction between SEPT7 and N-cadherin. Importantly, knockdown of SEPT7 decreased accumulation of N-cadherin aroundC. albicansin intact endothelial cells and reduced binding of N-cadherin to this organism, as revealed by the affinity purification assay. Furthermore, SEPT7 knockdown significantly inhibited the endocytosis ofC. albicans. Therefore, in response toC. albicansinfection, SEPT7 forms a complex with endothelial cell N-cadherin, is required for normal accumulation of N-cadherin aroundC. albicanshyphae, and is necessary for maximal endocytosis of the organism.IMPORTANCEDuring hematogenously disseminated infection,Candida albicansinvades the endothelial cell lining of the blood vessels to invade the deep tissues.C. albicanscan invade endothelial cells by inducing its own endocytosis, which is triggered when theC. albicansAls3 and Ssa1 invasins bind to N-cadherin on the endothelial cell surface. How this binding induces endocytosis is incompletely understood. Septins are intracellular GTP-binding proteins that influence the function and localization of cell surface proteins. We found thatC. albicansAls3 and Ssa1 bind to a complex containing N-cadherin and septin 7, which in turn interacts with endothelial cell microfilaments, thereby inducing endocytosis of the organism. The key role of septin 7 in governing receptor-mediated endocytosis is likely relevant to host cell invasion by other microbial pathogens, in addition toC. albicans.

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 AP-2-Dependent Endocytic Recycling of the Chitin Synthase Chs3 Regulates Polarized Growth inCandida albicans

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
H. C. Knafler ◽  
I. I. Smaczynska-de Rooij ◽  
L. A. Walker ◽  
K. K. Lee ◽  
N. A. R. Gow ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cell Surface ◽  
Hyphal Growth ◽  
Specific Cell ◽  
Polarized Growth ◽  
Endocytic Recycling ◽  
Content Type ◽  
Wall Deposition ◽  
Cell Wall Deposition

ABSTRACTThe human fungal pathogenCandida albicansis known to require endocytosis to enable its adaptation to diverse niches and to maintain its highly polarized hyphal growth phase. While studies have identified changes in transcription leading to the synthesis and secretion of new proteins to facilitate hyphal growth, effective maintenance of hyphae also requires concomitant removal or relocalization of other cell surface molecules. The key molecules which must be removed from the cell surface, and the mechanisms behind this, have, however, remained elusive. In this study, we show that the AP-2 endocytic adaptor complex is required for the internalization of the major cell wall biosynthesis enzyme Chs3. We demonstrate that this interaction is mediated by the AP-2 mu subunit (Apm4) YXXΦ binding domain. We also show that in the absence of Chs3 recycling via AP-2, cells have abnormal cell wall composition, defective polarized cell wall deposition, and morphological defects. The study also highlights key distinctions between endocytic requirements of growth at yeast buds compared to that at hyphal tips and different requirements of AP-2 in maintaining the polarity of mannosylated proteins and ergosterol at hyphal tips. Together, our findings highlight the importance of correct cell wall deposition in cell shape maintenance and polarized growth and the key regulatory role of endocytic recycling via the AP-2 complex.IMPORTANCECandida albicansis a human commensal yeast that can cause significant morbidity and mortality in immunocompromised individuals. Within humans,C. albicanscan adopt different morphologies as yeast or filamentous hyphae and can occupy different niches with distinct temperatures, pHs, CO2levels, and nutrient availability. Both morphological switching and growth in different environments require cell surface remodelling, which involves both the addition of newly synthesized proteins as well as the removal of other proteins. In our study, we demonstrate the importance of an adaptor complex AP-2 in internalizing and recycling a specific cell surface enzyme to maintain effective polarized hyphal growth. Defects in formation of the complex or in its ability to interact directly with cargo inhibit enzyme uptake and lead to defective cell walls and aberrant hyphal morphology. Our data indicate that the AP-2 adaptor plays a central role in regulating cell surface composition inCandida.

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.

Studying structure of Coronaviridae, analyzing their geometry and focusing on the role of electronic applications in health awareness of viruses

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Eman Almuhur ◽  
Manal Al-Labadi ◽  
Amani Shatarah ◽  
Nazneen Khan ◽  
Raeesa Bashir
Keyword(s):  
Human Body ◽  
Design Methodology ◽  
Health Technology ◽  
Content Type ◽  
Mathematical Structures ◽  
Infected People ◽  
Movement Mechanism ◽  
Effective Role ◽  
Health Applications

Purpose This study aims to focus on electronic applications that have an effective role in raising the awareness of the dangers of viruses’ transmission from person-to-person and their positive and important impact on people’s lives. Design/methodology/approach The authors illustrated the effects of socializing with infected people on a human body by a model in geometry and how the prospected antibiotic annihilates the structure of the virus. The authors discussed vital operations inside the human body to expound the geometry of objects that are closed under their operations, such as viruses, especially Coronaviridae. Findings Also, the authors discussed some of the e-health applications in Jordan. As e-health activities, programs and applications have been given attention, the authors focused on potentials for constructing strategies that lead to create a featuring health technology. Originality/value Moreover, in this study, the authors explored the structure and geometry of Coronaviridae family, especially coronavirus that causes lots of diseases, and explained its movement mechanism using the mathematical structures.

scholarly journals Role of Matrix β-1,3 Glucan in Antifungal Resistance of Non-albicans Candida Biofilms

2013 ◽  
Vol 57 (4) ◽  
pp. 1918-1920 ◽  
Author(s):  
K. F. Mitchell ◽  
H. T. Taff ◽  
M. A. Cuevas ◽  
E. L. Reinicke ◽  
H. Sanchez ◽  
...  
Keyword(s):  
Health Care ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Care Setting ◽  
Antifungal Susceptibility ◽  
Antifungal Drug ◽  
Content Type ◽  
The Matrix ◽  
Biofilm Matrix

ABSTRACTCandidabiofilm infections pose an increasing threat in the health care setting due to the drug resistance associated with this lifestyle. Several mechanisms underlie the resistance phenomenon. InCandida albicans, one mechanism involves drug impedance by the biofilm matrix linked to β-1,3 glucan. Here, we show this is important for otherCandidaspp. We identified β-1,3 glucan in the matrix, found that the matrix sequesters antifungal drug, and enhanced antifungal susceptibility with matrix β-1,3 glucan hydrolysis.

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