scholarly journals CAP1, an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

2001 ◽  
Vol 183 (10) ◽  
pp. 3211-3223 ◽  
Author(s):  
Yong-Sun Bahn ◽  
Paula Sundstrom
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Germ Tube ◽  
Filamentous Growth ◽  
Tube Formation ◽  
Camp Signaling ◽  
Solid Media ◽  
Opportunistic Fungal Pathogen ◽  
Camp Levels

ABSTRACT In response to a wide variety of environmental stimuli, the opportunistic fungal pathogen Candida albicans exits the budding cycle, producing germ tubes and hyphae concomitant with expression of virulence genes, such as that encoding hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP) increases in promoting bud-hypha transitions, but genetic evidence relating genes that control cAMP levels to bud-hypha transitions has not been reported. Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with Ras and adenylate cyclase to increase cAMP levels under specific environmental conditions. To initiate studies on the relationship between cAMP signaling and bud-hypha transitions in C. albicans, we identified, cloned, characterized, and disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1 budded in conditions that led to germ tube formation in isogenic strains withCAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha transitions and filamentous growth in thecap1/cap1 mutant in liquid and solid media, respectively, showing clearly that cAMP promotes hypha formation in C. albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans strains with deletions of both alleles ofCAP1 were avirulent in a mouse model of systemic candidiasis. The avirulence of a germ tube-deficientcap1/cap1 mutant coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1-mediated cAMP signaling pathway is required for bud-hypha transitions, filamentous growth, and the pathogenesis of candidiasis.

scholarly journals Arginine-Induced Germ Tube Formation in Candida albicans Is Essential for Escape from Murine Macrophage Line RAW 264.7

2009 ◽  
Vol 77 (4) ◽  
pp. 1596-1605 ◽  
Author(s):  
Suman Ghosh ◽  
Dhammika H. M. L. P. Navarathna ◽  
David D. Roberts ◽  
Jake T. Cooper ◽  
Audrey L. Atkin ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Germ Tube ◽  
Tube Formation ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Wild Type ◽  
Normal Flora ◽  
Opportunistic Fungal Pathogen ◽  
Germ Tubes

ABSTRACT The opportunistic fungal pathogen Candida albicans is a part of the normal flora but it also causes systemic candidiasis if it reaches the bloodstream. Upon being phagocytized by macrophages, an important component of innate immunity, C. albicans rapidly upregulates a set of arginine biosynthetic genes. Arginine, urea, and CO2 induced hyphae in a density-dependent manner in wild-type, cph1/cph1, and rim101/rim101 strains but not in efg1/efg1 or cph1/cph1 efg1/efg1 strains. Arginase (Car1p) converts arginine to urea, which in turn is degraded by urea amidolyase (Dur1,2p) to produce CO2, a signal for hyphal switching. We used a dur1,2/dur1,2 mutant (KWN6) and the complemented strain, KWN8 (dur1,2/dur1,2::DUR1,2/DUR1,2) to study germ tube formation. KWN6 could not make germ tubes in the presence of arginine or urea but did in the presence of 5% CO2, which bypasses Dur1,2p. We also tested the effect of arginine on the interaction between the macrophage line RAW 264.7 and several strains of C. albicans. Arginine activated an Efg1p-dependent yeast-to-hypha switch, enabling wild-type C. albicans and KWN8 to escape from macrophages within 6 h, whereas KWN6 was defective in this regard. Additionally, two mutants that cannot synthesize arginine, BWP17 and SN152, were defective in making hyphae inside the macrophages, whereas the corresponding arginine prototrophs, DAY286 and SN87, formed germ tubes and escaped from macrophages. Therefore, metabolism of arginine by C. albicans controls hyphal switching and provides an important mechanism for escaping host defense.

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 Actin Cytoskeletal Dynamics in Activation of the Cyclic AMP Pathway and HWP1 Gene Expression in Candida albicans

2007 ◽  
Vol 6 (10) ◽  
pp. 1824-1840 ◽  
Author(s):  
Michael J. Wolyniak ◽  
Paula Sundstrom
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Cyclic Amp ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Specific Gene ◽  
Camp Signaling Pathway ◽  
Hypha Formation ◽  
Cytoskeletal Dynamics ◽  
Opportunistic Fungal Pathogen

ABSTRACT Changes in gene expression during reversible bud-hypha transitions of the opportunistic fungal pathogen Candida albicans permit adaptation to environmental conditions that are critical for proliferation in host tissues. Our previous work has shown that the hypha-specific adhesin gene HWP1 is up-regulated by the cyclic AMP (cAMP) signaling pathway. However, little is known about the potential influences of determinants of cell morphology on HWP1 gene expression. We found that blocking hypha formation with cytochalasin A, which destabilizes actin filaments, and with latrunculin A, which sequesters actin monomers, led to a loss of HWP1 gene expression. In contrast, high levels of HWP1 gene expression were observed when the F-actin stabilizer jasplakinolide was used to block hypha formation, suggesting that HWP1 expression could be regulated by actin structures. Mutants defective in formin-mediated nucleation of F-actin were reduced in HWP1 gene expression, providing genetic support for the importance of actin structures. Kinetic experiments with wild-type and actin-deficient cells revealed two distinct phases of HWP1 gene expression, with a slow, actin-independent phase preceding a fast, actin-dependent phase. Low levels of HWP1 gene expression that appeared to be independent of stabilized actin and cAMP signaling were detected using indirect immunofluorescence. A connection between actin structures and the cAMP signaling pathway was shown using hyper- and hypomorphic cAMP mutants, providing a possible mechanism for up-regulation of HWP1 gene expression by stabilized actin. The results reveal a new role for F-actin as a regulatory agent of hypha-specific gene expression at the bud-hypha transition.

Candida albicans growth and germ tube formation can be inhibited by simple diphenyl diselenides [(PhSe)2, (MeOPhSe)2, (p-Cl-PhSe)2, (F3CPhSe)2] and diphenyl ditelluride

Mycoses ◽  
2010 ◽  
Vol 54 (6) ◽  
pp. 506-513 ◽  
Author(s):  
Isabela Bueno Rosseti ◽  
Caroline Wagner ◽  
Roselei Fachinetto ◽  
Paulo Taube Junior ◽  
Maricilia Silva Costa
Keyword(s):  
Candida Albicans ◽  
Germ Tube ◽  
Tube Formation ◽  
Diphenyl Ditelluride

scholarly journals Satureja khuzistanica Jamzad essential oil and its anti-candidal activities against clinical isolates of Candida albicans isolated from women with candidiasis

Infectio ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 16 ◽  
Author(s):  
Mohaddese Mahboubi ◽  
Bahareh Attaran
Keyword(s):  
Candida Albicans ◽  
Essential Oil ◽  
Germ Tube ◽  
Folk Medicine ◽  
Tube Formation ◽  
Clinical Isolates ◽  
Analgesic Agent ◽  
Aerial Parts ◽  
Main Component ◽  
Cytoplasmic Structures

Satureja khuzistanica Jamzad is known as antiseptic and analgesic agent in folk medicine. The aim of this investigation was to evaluate the anti-candidal activity of S. khuzistanica aerial parts essential oil against clinical isolates of Candida albicans, which were isolated from women with chronic recurrent candidiasis. For this purpose, the chemical composition of hydro-distilled essential oil was determined by GC and GC-MS analysis. Then, the anti-candidal activity of essential oil and its main component (carvacrol) were determined. Carvacrol (94.1%) was the main component of essential oil, followed by β-bisabolene, p-cymene and γ-terpinene. S. khuzistanica essential oil had strong anti-candidal activity against clinical isolates of C. albicans via inhibition of germ tube formation and induction the huge punctures in the cytoplasmic structures. The cell membranes were intact in presence of essential oil or carvacrol. S. khuzistanica essential oil as the main source of carvacrol can be used for treatment of C. albicans related infections.

scholarly journals Enzymes of N-Acetylglucosamine Metabolism during Germ-tube Formation in Candida albicans

Microbiology ◽  
1982 ◽  
Vol 128 (10) ◽  
pp. 2319-2326 ◽  
Author(s):  
P. Gopal ◽  
P. A. Sullivan ◽  
M. G. Shepherd
Keyword(s):  
Candida Albicans ◽  
Germ Tube ◽  
Tube Formation
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