UV009 The human pathogenic yeast Candida glabrata: characterisation of the cell wall architecture and identification of cell wall proteins

2003 ◽  
Vol 293 ◽  
pp. 127
Keyword(s):  
Cell Wall ◽  
Candida Glabrata ◽  
Cell Wall Proteins ◽  
Pathogenic Yeast ◽  
Cell Wall Architecture

scholarly journals A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata

2007 ◽  
Vol 104 (18) ◽  
pp. 7628-7633 ◽  
Author(s):  
Rupinder Kaur ◽  
Biao Ma ◽  
Brendan P. Cormack
Keyword(s):  
Cell Wall ◽  
Mammalian Cells ◽  
Candida Glabrata ◽  
Global Changes ◽  
Cell Wall Proteins ◽  
Culture Model ◽  
Genes Encoding ◽  
Tissue Culture Model ◽  
A Cell ◽  
Aspartyl Proteases

Candida glabrata is a yeast pathogen of humans. We have established a tissue culture model to analyze the interaction of C. glabrata with macrophages. Transcript profiling of yeast ingested by macrophages reveals global changes in metabolism as well as increased expression of a gene family (YPS genes) encoding extracellular glycosylphosphatidylinositol-linked aspartyl proteases. Eight of these YPS genes are found in a cluster that is unique to C. glabrata. Genetic analysis shows that the C. glabrata YPS genes are required for cell wall integrity, adherence to mammalian cells, survival in macrophages and virulence. By monitoring the processing of a cell wall adhesin, Epa1, we also show that Yps proteases play an important role in cell wall re-modeling by removal and release of glycosylphosphatidylinositol-anchored cell wall proteins.

scholarly journals Essential Role for the Phosphatidylinositol 3,5-Bisphosphate Synthesis Complex in Caspofungin Tolerance and Virulence in Candida glabrata

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Deepak Kumar Choudhary ◽  
Priyanka Bhakt ◽  
Rupinder Kaur
Keyword(s):  
Cell Wall ◽  
Candida Glabrata ◽  
Scaffolding Protein ◽  
Pathogenic Yeast ◽  
Lipid Kinase ◽  
Lipid Molecule ◽  
Content Type ◽  
Phosphoinositide Signaling ◽  
Promising Target ◽  
Opportunistic Fungal Pathogen

ABSTRACT Increasing resistance of the human opportunistic fungal pathogen Candida glabrata toward the echinocandin antifungals, which target the cell wall, is a matter of grave clinical concern. Echinocandin resistance in C. glabrata has primarily been associated with mutations in the β-glucan synthase-encoding genes C. glabrata FKS1 (CgFKS1) and CgFKS2. This notwithstanding, the role of the phosphoinositide signaling in antifungal resistance is just beginning to be deciphered. The phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance lipid molecule that is pivotal to the intracellular membrane traffic. Here, we demonstrate for the first time that the PI(3,5)P2 kinase CgFab1, along with its activity regulator CgVac7 and the scaffolding protein CgVac14, is required for maintenance of the cell wall chitin content, survival of the cell wall, and caspofungin stress. Further, deletion analyses implicated the PI(3,5)P2 phosphatase CgFig4 in the regulation of PI(3,5)P2 levels and azole and echinocandin tolerance through CgVac14. We also show the localization of the CgFab1 lipid kinase to the vacuole to be independent of the CgVac7, CgVac14, and CgFig4 proteins. Lastly, our data demonstrate an essential requirement for PI(3,5)P2 signaling components, CgFab1, CgVac7, and CgVac14, in the intracellular survival and virulence in C. glabrata. Altogether, our data have yielded key insights into the functions and metabolism of PI(3,5)P2 lipid in the pathogenic yeast C. glabrata. In addition, our data highlight that CgVac7, whose homologs are absent in higher eukaryotes, may represent a promising target for antifungal therapy.

scholarly journals Copper Acts Synergistically with Fluconazole in Candida glabrata by Compromising Drug Efflux, Sterol Metabolism, and Zinc Homeostasis

2021 ◽  
Author(s):  
Ana Gaspar-Cordeiro ◽  
Catarina Amaral ◽  
Vania Pobre ◽  
Wilson Antunes ◽  
Ana Petronilho ◽  
...  
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Candida Glabrata ◽  
Zinc Homeostasis ◽  
Ergosterol Biosynthesis ◽  
Gene Encoding ◽  
Pathogenic Yeast ◽  
Transcription Regulator ◽  
Opportunistic Pathogenic ◽  
Irregular Cell

The synergistic combinations of drugs are promising strategies to boost the effectiveness of current antifungals and thus prevent the emergence of resistance. In this work, we show that copper and the antifungal fluconazole act synergistically against Candida glabrata, an opportunistic pathogenic yeast intrinsically tolerant to fluconazole. Analyses of the transcriptomic profile of C. glabrata after the combination of copper and fluconazole showed that the expression of the multidrug transporter gene CDR1 was decreased, suggesting that fluconazole efflux could be affected. In agreement, we observed that copper inhibits the transactivation of Pdr1, the transcription regulator of multidrug transporters, and leads to the intracellular accumulation of fluconazole. Copper also decreases the transcriptional induction of ergosterol biosynthesis (ERG) genes by fluconazole, which culminates in the accumulation of toxic sterols. Co-treatment of cells with copper and fluconazole should affect the function of proteins located in the plasma membrane, as several ultrastructural alterations, including irregular cell wall and plasma membrane and loss of cell wall integrity, were observed. Finally, we show that the combination of copper and fluconazole downregulates the expression of the gene encoding the zinc-responsive transcription regulator Zap1, which possibly, together with the membrane transporters malfunction, generates zinc depletion. Supplementation with zinc reverts the toxic effect of combining copper with fluconazole, underscoring the importance of this metal in the observed synergistic effect. Overall, this work, while unveiling the molecular basis that supports the use of copper to enhance the effectiveness of fluconazole, paves the way for the development of new metal-based antifungal strategies.

Structural study of a cell wall mannan-protein complex of the pathogenic yeast Candida glabrata IFO 0622 strain

1992 ◽  
Vol 294 (2) ◽  
pp. 662-669 ◽  
Author(s):  
Hidemitsu Kobayashi ◽  
Hideko Mitobe ◽  
Kaori Takahashi ◽  
Takayuki Yamamoto ◽  
Nobuyuki Shibata ◽  
...  
Keyword(s):  
Cell Wall ◽  
Structural Study ◽  
Protein Complex ◽  
Candida Glabrata ◽  
Pathogenic Yeast ◽  
A Cell ◽  
Cell Wall Mannan

scholarly journals Differential cell wall remodeling of two chitin synthase deletants Δchs3A and Δchs3B in the pathogenic yeast Candida glabrata

2011 ◽  
Vol 11 (5) ◽  
pp. 398-407 ◽  
Author(s):  
Keigo Ueno ◽  
Yuichi Namiki ◽  
Hiroki Mitani ◽  
Masashi Yamaguchi ◽  
Hiroji Chibana
Keyword(s):  
Cell Wall ◽  
Candida Glabrata ◽  
Chitin Synthase ◽  
Pathogenic Yeast ◽  
Cell Wall Remodeling ◽  
Differential Cell

scholarly journals A novel class of Candida glabrata cell wall proteins with β-helix fold mediates adhesion in clinical isolates

2021 ◽  
Vol 17 (12) ◽  
pp. e1009980
Author(s):  
Viktoria Reithofer ◽  
Jordan Fernández-Pereira ◽  
María Alvarado ◽  
Piet de Groot ◽  
Lars-Oliver Essen
Keyword(s):  
Cell Wall ◽  
Candida Glabrata ◽  
Sequence Similarity ◽  
Domain Architecture ◽  
Surface Characteristics ◽  
Structural Similarity ◽  
Cell Aggregation ◽  
Phenotypic Analysis ◽  
Pathogenic Yeast ◽  
Opportunistic Pathogenic

Candida glabrata is an opportunistic pathogenic yeast frequently causing infections in humans. Though it lacks typical virulence factors such as hyphal development, C. glabrata contains a remarkably large and diverse set of putative wall adhesins that is crucial for its success as pathogen. Here, we present an analysis of putative adhesins from the homology clusters V and VI. First, sequence similarity network analysis revealed relationships between cluster V and VI adhesins and S. cerevisiae haze protective factors (Hpf). Crystal structures of A-domains from cluster VI adhesins Awp1 and Awp3b reveal a parallel right-handed β-helix domain that is linked to a C-terminal β-sandwich. Structure solution of the A-region of Awp3b via single wavelength anomalous diffraction phasing revealed the largest known lanthanide cluster with 21 Gd3+ ions. Awp1-A and Awp3b-A show structural similarity to pectate lyases but binding to neither carbohydrates nor Ca2+ was observed. Phenotypic analysis of awp1Δ, awp3Δ, and awp1,3Δ double mutants did also not confirm their role as adhesins. In contrast, deletion mutants of the cluster V adhesin Awp2 in the hyperadhesive clinical isolate PEU382 demonstrated its importance for adhesion to polystyrene or glass, biofilm formation, cell aggregation and other cell surface-related phenotypes. Together with cluster III and VII adhesins our study shows that C. glabrata CBS138 can rely on a set of 42 Awp1-related adhesins with β-helix/α-crystallin domain architecture for modifying the surface characteristics of its cell wall.

scholarly journals Physiologically Relevant Alternative Carbon Sources Modulate Biofilm Formation, Cell Wall Architecture, and the Stress and Antifungal Resistance of Candida glabrata

2019 ◽  
Vol 20 (13) ◽  
pp. 3172 ◽  
Author(s):  
Shu Yih Chew ◽  
Kok Lian Ho ◽  
Yoke Kqueen Cheah ◽  
Doblin Sandai ◽  
Alistair J.P. Brown ◽  
...  
Keyword(s):  
Cell Wall ◽  
Carbon Metabolism ◽  
Candida Glabrata ◽  
Fungal Pathogens ◽  
Carbon Sources ◽  
Carbon Assimilation ◽  
Biofilm Growth ◽  
Specific Host ◽  
The Impact ◽  
Cell Wall Architecture

Flexibility in carbon metabolism is pivotal for the survival and propagation of many human fungal pathogens within host niches. Indeed, flexible carbon assimilation enhances pathogenicity and affects the immunogenicity of Candida albicans. Over the last decade, Candida glabrata has emerged as one of the most common and problematic causes of invasive candidiasis. Despite this, the links between carbon metabolism, fitness, and pathogenicity in C. glabrata are largely unexplored. Therefore, this study has investigated the impact of alternative carbon metabolism on the fitness and pathogenic attributes of C. glabrata. We confirm our previous observation that growth on carbon sources other than glucose, namely acetate, lactate, ethanol, or oleate, attenuates both the planktonic and biofilm growth of C. glabrata, but that biofilms are not significantly affected by growth on glycerol. We extend this by showing that C. glabrata cells grown on these alternative carbon sources undergo cell wall remodeling, which reduces the thickness of their β-glucan and chitin inner layer while increasing their outer mannan layer. Furthermore, alternative carbon sources modulated the oxidative stress resistance of C. glabrata as well as the resistance of C. glabrata to an antifungal drug. In short, key fitness and pathogenic attributes of C. glabrata are shown to be dependent on carbon source. This reaffirms the perspective that the nature of the carbon sources available within specific host niches is crucial for C. glabrata pathogenicity during infection.

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