scholarly journals Carnitine-Dependent Transport of Acetyl Coenzyme A in Candida albicans Is Essential for Growth on Nonfermentable Carbon Sources and Contributes to Biofilm Formation

2008 ◽  
Vol 7 (4) ◽  
pp. 610-618 ◽  
Author(s):  
Karin Strijbis ◽  
Carlo W. T. van Roermund ◽  
Wouter F. Visser ◽  
Els C. Mol ◽  
Janny van den Burg ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fatty Acid ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Carbon Sources ◽  
Acetyl Coa ◽  
Oxidation Activity ◽  
Acetyl Coenzyme A ◽  
Human Fungal Pathogen ◽  
Peroxisomal Fatty Acid

ABSTRACT In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid β-oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae; one is dependent on peroxisomal citrate synthase (Cit), while the other requires peroxisomal and mitochondrial carnitine acetyltransferase (Cat) activities. Here we show that the human fungal pathogen Candida albicans lacks peroxisomal Cit, relying exclusively on Cat activity for transport of acetyl units. Deletion of the CAT2 gene encoding the major Cat enzyme in C. albicans resulted in a strain that had lost both peroxisomal and mitochondrion-associated Cat activities, could not grow on fatty acids or C2 carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA, and showed greatly reduced fatty acid β-oxidation activity. The cat2 null mutant was, however, not attenuated in virulence in a mouse model of systemic candidiasis. These observations support our previous results showing that peroxisomal fatty acid β-oxidation activity is not essential for C. albicans virulence. Biofilm formation by the cat2 mutant on glucose was slightly reduced compared to that by the wild type, although both strains grew at the same rate on this carbon source. Our data show that C. albicans has diverged considerably from S. cerevisiae with respect to the mechanism of intracellular acetyl-CoA transport and imply that carnitine dependence may be an important trait of this human fungal pathogen.

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 Antifungal effects of alantolactone on Candida albicans: an in vitro study

2021 ◽  
Author(s):  
Xin Liu ◽  
Lili Zhong ◽  
Zhiming Ma ◽  
Yujie Sui ◽  
Jia’nan Xie ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Medical Devices ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
In Vitro Study ◽  
Antifungal Drugs ◽  
Promising Candidate ◽  
Human Fungal Pathogen ◽  
Antifungal Effects

AbstractThe human fungal pathogen Candida albicans can cause many kinds of infections, including biofilm infections on medical devices, while the available antifungal drugs are limited to only a few. In this study, alantolactone (Ala) demonstrated antifungal activities against C. albicans, as well as other Candida species, with a MIC of 72 μg/mL. Ala could also inhibit the adhesion, yeast-to-hyphal transition, biofilm formation and development of C. albicans. The exopolysaccharide of biofilm matrix and extracellular phospholipase production could also be reduced by Ala treatment. Ala could increase permeability of C. albicans cell membrane and ROS contribute to the antifungal activity of Ala. Overall, the present study suggests that Ala may provide a promising candidate for developing antifungal drugs against C. albicans infections.

scholarly journals Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of Candida albicans

2006 ◽  
Vol 5 (11) ◽  
pp. 1847-1856 ◽  
Author(s):  
Katarzyna Piekarska ◽  
Els Mol ◽  
Marlene van den Berg ◽  
Guy Hardy ◽  
Janny van den Burg ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Candida Albicans ◽  
Fatty Acid ◽  
Glyoxylate Cycle ◽  
Carbon Sources ◽  
Phagocytic Cells ◽  
Fungal Virulence ◽  
Oxidation Pathway ◽  
Virulence Attenuation ◽  
Peroxisomal Fatty Acid

ABSTRACT Phagocytic cells form the first line of defense against infections by the human fungal pathogen Candida albicans. Recent in vitro gene expression data suggest that upon phagocytosis by macrophages, C. albicans reprograms its metabolism to convert fatty acids into glucose by inducing the enzymes of the glyoxylate cycle and fatty acid β-oxidation pathway. Here, we asked whether fatty acid β-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5Δ/pex5Δ mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2Δ/fox2Δ mutant, which lacks the second enzyme of the β-oxidation pathway. Both mutant strains had strongly reduced β-oxidation activity and, accordingly, were unable to grow on media with fatty acids as a sole carbon source. Surprisingly, only the fox2Δ/fox2Δ mutant, and not the pex5Δ/pex5Δ mutant, displayed strong growth defects on nonfermentable carbon sources other than fatty acids (e.g., acetate, ethanol, or lactate) and showed attenuated virulence in a mouse model for systemic candidiasis. The degree of virulence attenuation of the fox2Δ/fox2Δ mutant was comparable to that of the icl1Δ/icl1Δ mutant, which lacks a functional glyoxylate cycle and also fails to grow on nonfermentable carbon sources. Together, our data suggest that peroxisomal fatty acid β-oxidation is not essential for virulence of C. albicans, implying that the attenuated virulence of the fox2Δ/fox2Δ mutant is largely due to a dysfunctional glyoxylate cycle.

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

2019 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Untreated Control ◽  
Morphological Transition ◽  
Yeast Form ◽  
Polystyrene Surface ◽  
Human Fungal Pathogen ◽  
Morphological Transitions ◽  
Simple Carbohydrate

Abstract The opportunistic human fungal pathogen Candida albicans rely 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 morphological switching 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 Role of Acetyl Coenzyme A Synthesis and Breakdown in Alternative Carbon Source Utilization in Candida albicans

2008 ◽  
Vol 7 (10) ◽  
pp. 1733-1741 ◽  
Author(s):  
Aaron J. Carman ◽  
Slavena Vylkova ◽  
Michael C. Lorenz
Keyword(s):  
Fatty Acids ◽  
Candida Albicans ◽  
Coenzyme A ◽  
Glyoxylate Cycle ◽  
Functional Divergence ◽  
Carbon Sources ◽  
Growth Defect ◽  
Acetyl Coa ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme

ABSTRACT Acetyl coenzyme A (acetyl-CoA) is the central intermediate of the pathways required to metabolize nonfermentable carbon sources. Three such pathways, i.e., gluconeogenesis, the glyoxylate cycle, and β-oxidation, are required for full virulence in the fungal pathogen Candida albicans. These processes are compartmentalized in the cytosol, mitochondria, and peroxosomes, necessitating transport of intermediates across intracellular membranes. Acetyl-CoA is trafficked in the form of acetate by the carnitine shuttle, and we hypothesized that the enzymes that convert acetyl-CoA to/from acetate, i.e., acetyl-CoA hydrolase (ACH1) and acetyl-CoA synthetase (ACS1 and ACS2), would regulate alternative carbon utilization and virulence. We show that C. albicans strains depleted for ACS2 are unviable in the presence of most carbon sources, including glucose, acetate, and ethanol; these strains metabolize only fatty acids and glycerol, a substantially more severe phenotype than that of Saccharomyces cerevisiae acs2 mutants. In contrast, deletion of ACS1 confers no phenotype, though it is highly induced in the presence of fatty acids, perhaps explaining why acs2 mutants can utilize fatty acids. Strains lacking ACH1 have a mild growth defect on some carbon sources but are fully virulent in a mouse model of disseminated candidiasis. Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. Together, these results show that acetyl-CoA metabolism and transport are critical for growth of C. albicans on a wide variety of nutrients. Furthermore, the phenotypic differences between mutations in these highly conserved genes in S. cerevisiae and C. albicans support recent findings that significant functional divergence exists even in fundamental metabolic pathways between these related yeasts.

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

2019 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Untreated Control ◽  
Morphological Transition ◽  
Yeast Form ◽  
Polystyrene Surface ◽  
Human Fungal Pathogen ◽  
Morphological Transitions ◽  
Simple Carbohydrate

Abstract The opportunistic human fungal pathogen Candida albicans rely 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 morphological switching 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 pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal Pathogen Candida albicans

2017 ◽  
Vol 8 ◽  
Author(s):  
Julien Chaillot ◽  
Faiza Tebbji ◽  
Carlos García ◽  
Hugo Wurtele ◽  
René Pelletier ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Fungal Pathogen ◽  
Human Fungal Pathogen

An improved transformation protocol for the human fungal pathogen Candida albicans

2003 ◽  
Vol 42 (6) ◽  
pp. 339-343 ◽  
Author(s):  
Andrea Walther ◽  
Jürgen Wendland
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Transformation Protocol ◽  
Human Fungal Pathogen

scholarly journals Pmt-Mediated O Mannosylation Stabilizes an Essential Component of the Secretory Apparatus, Sec20p, in Candida albicans

2004 ◽  
Vol 3 (5) ◽  
pp. 1164-1168 ◽  
Author(s):  
Yvonne Weber ◽  
Stephan K.-H. Prill ◽  
Joachim F. Ernst
Keyword(s):  
Endoplasmic Reticulum ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Wild Type ◽  
Rapid Degradation ◽  
Vesicle Traffic ◽  
Human Fungal Pathogen ◽  
Low Levels ◽  
Lumenal Domain ◽  
Secretory Apparatus

ABSTRACT Sec20p is an essential endoplasmic reticulum (ER) membrane protein in yeasts, functioning as a tSNARE component in retrograde vesicle traffic. We show that Sec20p in the human fungal pathogen Candida albicans is extensively O mannosylated by protein mannosyltransferases (Pmt proteins). Surprisingly, Sec20p occurs at wild-type levels in a pmt6 mutant but at very low levels in pmt1 and pmt4 mutants and also after replacement of specific Ser/Thr residues in the lumenal domain of Sec20p. Pulse-chase experiments revealed rapid degradation of unmodified Sec20p (38.6 kDa) following its biosynthesis, while the stable O-glycosylated form (50 kDa) was not formed in a pmt1 mutant. These results suggest a novel function of O mannosylation in eukaryotes, in that modification by specific Pmt proteins will prevent degradation of ER-resident membrane proteins via ER-associated degradation or a proteasome-independent pathway.

scholarly journals The 5’ untranslated region of theEFG1transcript promotes its translation to regulate hyphal morphogenesis inCandida albicans

2018 ◽  
Author(s):  
Prashant R. Desai ◽  
Klaus Lengeler ◽  
Mario Kapitan ◽  
Silas Matthias Janßen ◽  
Paula Alepuz ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Regulatory Mechanisms ◽  
Untranslated Regions ◽  
Regulatory Sequence ◽  
Transcriptional Level ◽  
Human Fungal Pathogen ◽  
Hyphal Morphogenesis ◽  
Cellular Morphogenesis ◽  
Incandida Albicans

ABSTRACTExtensive 5’ untranslated regions (UTR) are a hallmark of transcripts determining hyphal morphogenesis inCandida albicans.The major transcripts of theEFG1gene, which are responsible for cellular morphogenesis and metabolism, contain a 5’ UTR of up to 1170 nt. Deletion analyses of the 5’ UTR revealed a 218 nt sequence that is required for production of the Efg1 protein and its functions in filamentation, without lowering the level and integrity of theEFG1transcript. Polysomal analyses revealed that the 218 nt 5’ UTR sequence is required for efficient translation of the Efg1 protein. Replacement of theEFG1ORF by the heterologous reporter geneCaCBGlucconfirmed the positive regulatory importance of the identified 5’ UTR sequence. In contrast to other reported transcripts containing extensive 5’ UTR sequences, these results indicate the positive translational function of the 5’ UTR sequence in theEFG1transcript, which is observed in context of the nativeEFG1promoter. The results suggest that the 5’ UTR recruits regulatory factors, possibly during emergence of the native transcript, which aid in translation of theEFG1transcript.IMPORTANCEMany of the virulence traits that makeCandida albicansan important human fungal pathogen are regulated on a transcriptional level. Here we report an important regulatory contribution of translation, which is exerted by the extensive 5’ untranslated regulatory sequence (5’ UTR) of the transcript for the protein Efg1, which determines growth, metabolism and filamentation in the fungus. Presence of the 5’ UTR is required for efficient translation of Efg1, to promote filamentation. Because transcripts for many relevant regulators contain extensive 5’ UTR sequences, it appears that virulence ofC. albicansdepends on the combination of transcriptional and translation regulatory mechanisms.

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