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 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 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.

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