scholarly journals PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion

Microbiology ◽  
2010 ◽  
Vol 156 (8) ◽  
pp. 2484-2494 ◽  
Author(s):  
Julia Calderon ◽  
Martin Zavrel ◽  
Enrico Ragni ◽  
William A. Fonzi ◽  
Steffen Rupp ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Crucial Role ◽  
Extracellular Enzymes ◽  
Hyphal Growth ◽  
Fungal Cell ◽  
Cell Monolayers ◽  
Cell Wall Assembly ◽  
Abiotic Surfaces ◽  
Wall Assembly

The fungal cell wall plays a crucial role in host–pathogen interactions. Its formation is the result of the coordinated activity of several extracellular enzymes, which assemble the constituents, and remodel and hydrolyse them in the extracellular space. Candida albicans Phr1 and Phr2 proteins belong to family GH72 of the β-(1,3)-glucanosyltransferases and play a crucial role in cell wall assembly. PHR1 and PHR2, homologues of Saccharomyces cerevisiae GAS1, are differently regulated by extracellular pH. PHR1 is expressed when ambient pH is 5.5 or higher, whereas PHR2 has the reverse expression pattern. Their deletion causes a pH-conditional defect in morphogenesis and virulence. In this work we explored whether PHR1 deletion affects the ability of C. albicans to adhere to and invade human epithelia. PHR1 null mutants exhibited a marked reduction in adhesion to both abiotic surfaces and epithelial cell monolayers. In addition, the mutant was unable to penetrate and invade reconstituted human epithelia. Transcription profiling of selected hyphal-specific and adhesin-encoding genes indicated that in the PHR1 null mutant, HWP1 and ECE1 transcript levels were similarly reduced in both adhesion and suspension conditions. These results, combined with microscopy analysis of the septum position, suggest that PHR1 is not required for the induction of hyphal development but plays a key role in the maintenance of hyphal growth. Thus, the β-(1,3)-glucan processing catalysed by Phr1p is of fundamental importance in the maintenance of the morphological state on which the adhesive and invasive properties of C. albicans greatly depend.

scholarly journals Large-Scale Identification of Putative Exported Proteins in Candida albicans by Genetic Selection

2002 ◽  
Vol 1 (4) ◽  
pp. 514-525 ◽  
Author(s):  
L. Monteoliva ◽  
M. López Matas ◽  
C. Gil ◽  
C. Nombela ◽  
J. Pla
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Mammalian Cells ◽  
Large Scale ◽  
Extracellular Enzymes ◽  
Genetic Selection ◽  
Membrane Receptors ◽  
Open Reading Frames ◽  
Secreted Proteins ◽  
Fungal Cell

ABSTRACT In all living organisms, secreted proteins play essential roles in different processes. Of special interest is the construction of the fungal cell wall, since this structure is absent from mammalian cells. The identification of the proteins involved in its biogenesis is therefore a primary goal in antifungal research. To perform a systematic identification of such proteins in Candida albicans, we carried out a genetic screening in which in-frame fusions with an intracellular allele of invertase gene SUC2 of Saccharomyces cerevisiae can be used to select and identify putatively exported proteins in the heterologous host S. cerevisiae. Eighty-three clones were selected, including 11 previously identified genes from C. albicans as well as 41 C. albicans genes that encode proteins homologous to already described proteins from related organisms. They include enzymes involved in cell wall synthesis and protein secretion. We also found membrane receptors and transporters presumably related to the interaction of C. albicans with the environment as well as extracellular enzymes and proteins involved in different morphological transitions. In addition, 11 C. albicans open reading frames (ORFs) identified in this screening encode proteins homologous to unknown or putative proteins, while 5 ORFs encode novel secreted proteins without known homologues in other organisms. This screening procedure therefore not only identifies a set of targets of interest in antifungal research but also provides new clues for understanding the topological locations of many proteins involved in processes relevant to the pathogenicity of this microorganism.

scholarly journals ChsVb, a Class VII Chitin Synthase Involved in Septation, Is Critical for Pathogenicity in Fusarium oxysporum

2007 ◽  
Vol 7 (1) ◽  
pp. 112-121 ◽  
Author(s):  
Magdalena Martín-Urdíroz ◽  
M. Isabel G. Roncero ◽  
José Antonio González-Reyes ◽  
Carmen Ruiz-Roldán
Keyword(s):  
Cell Wall ◽  
Fusarium Oxysporum ◽  
Tomato Fruit ◽  
Infection Process ◽  
Chitin Synthase ◽  
Fungal Cell ◽  
Myosin Motor ◽  
Cell Wall Assembly ◽  
Chitin Synthases ◽  
Wall Assembly

ABSTRACT A new myosin motor-like chitin synthase gene, chsVb, has been identified in the vascular wilt fungus Fusarium oxysporum f. sp. lycopersici. Phylogenetic analysis of the deduced amino acid sequence of the chsVb chitin synthase 2 domain (CS2) revealed that ChsVb belongs to class VII chitin synthases. The ChsVb myosin motor-like domain (MMD) is shorter than the MMD of class V chitin synthases and does not contain typical ATP-binding motifs. Targeted disrupted single (ΔchsVb) and double (ΔchsV ΔchsVb) mutants were unable to infect and colonize tomato plants or grow invasively on tomato fruit tissue. These strains were hypersensitive to compounds that interfere with fungal cell wall assembly, produced lemon-like shaped conidia, and showed swollen balloon-like structures in hyphal subapical regions, thickened walls, aberrant septa, and intrahyphal hyphae. Our results suggest that the chsVb gene is likely to function in polarized growth and confirm the critical importance of cell wall integrity in the complex infection process of this fungus.

scholarly journals A Conserved Machinery Underlies the Synthesis of a Chitosan Layer in the Candida Chlamydospore Cell Wall

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Leo D. Bemena ◽  
Kyunghun Min ◽  
James B. Konopka ◽  
Aaron M. Neiman
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Drug Targets ◽  
Therapeutic Strategies ◽  
Effective Strategy ◽  
Fungal Cell ◽  
Detailed Understanding ◽  
Cell Wall Assembly ◽  
Wall Assembly ◽  
Potential Drug Targets

The cell wall is the interface between the fungal cell and its environment and disruption of cell wall assembly is an effective strategy for antifungal therapies. Therefore, a detailed understanding of how cell walls form is critical to identify potential drug targets and develop therapeutic strategies.

scholarly journals Pneumocystis carinii BCK1functions in a mitogen-activated protein kinase cascade regulating fungal cell-wall assembly

FEBS Letters ◽  
2003 ◽  
Vol 548 (1-3) ◽  
pp. 59-68 ◽  
Author(s):  
Charles F. Thomas ◽  
Pawan K. Vohra ◽  
John G. Park ◽  
Veenu Puri ◽  
Andrew H. Limper ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protein Kinase ◽  
Pneumocystis Carinii ◽  
Mitogen Activated Protein Kinase ◽  
Fungal Cell ◽  
Cell Wall Assembly ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Wall Assembly ◽  
Protein Kinase Cascade

scholarly journals Medicinal genetics approach towards identifying the molecular target of a novel inhibitor of fungal cell wall assembly

2003 ◽  
Vol 48 (4) ◽  
pp. 1029-1042 ◽  
Author(s):  
Kappei Tsukahara ◽  
Katsura Hata ◽  
Kazutaka Nakamoto ◽  
Koji Sagane ◽  
Nao-aki Watanabe ◽  
...  
Keyword(s):  
Cell Wall ◽  
Molecular Target ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Cell Wall Assembly ◽  
Wall Assembly

scholarly journals Bgs3p, a Putative 1,3-β-Glucan Synthase Subunit, Is Required for Cell Wall Assembly in Schizosaccharomyces pombe

2003 ◽  
Vol 2 (1) ◽  
pp. 159-169 ◽  
Author(s):  
Victoria Martín ◽  
Blanca García ◽  
Elena Carnero ◽  
Angel Durán ◽  
Yolanda Sánchez
Keyword(s):  
Cell Wall ◽  
Fission Yeast ◽  
Green Fluorescence Protein ◽  
Cell Wall Biosynthesis ◽  
Calcofluor White ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Cell Wall Assembly ◽  
Main Components ◽  
Wall Assembly

ABSTRACT β-Glucans are the main components of the fungal cell wall. Fission yeast possesses a family of β-glucan synthase-related genes. We describe here the cloning and characterization of bgs3 +, a new member of this family. bgs3 + was cloned as a suppressor of a mutant hypersensitive to Echinocandin and Calcofluor White, drugs that interfere with cell wall biosynthesis. Disruption of the gene is lethal, and a decrease in Bgs3p levels leads to rounded cells with thicker walls, slightly reduces the amount of the β-glucan, and raises the amount of α-glucan polymer. These cells finally died. bgs3 + is expressed in vegetative cells grown in different conditions and during mating and germination and is not enhanced by stress situations. Consistent with the observed expression pattern, Bgs3-green fluorescence protein (GFP-Bgs3p) was found at the growing tips during interphase and at the septum prior to cytokinesis, always localized to growth areas. We also found GFP-Bgs3p in mating projections, during the early stages of zygote formation, and at the growing pole during ascospore germination. We conclude that Bgs3p localization is restricted to growth areas and that Bgs3p is a glucan synthase homologue required for cell wall biosynthesis and cell elongation in the fission yeast life cycle.

scholarly journals Molecular mechanisms of fungal cell-wall assembly

2010 ◽  
Vol 66 (a1) ◽  
pp. s32-s32
Author(s):  
Alex Schuettelkopf ◽  
Daan van Aalten ◽  
Helge Dorfmueller
Keyword(s):  
Cell Wall ◽  
Molecular Mechanisms ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Cell Wall Assembly ◽  
Wall Assembly

scholarly journals The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans

2021 ◽  
Author(s):  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Gumieniczek ◽  
Maria Malm ◽  
Krzysztof Z. Łączkowski ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Mode Of Action ◽  
Thiazole Derivatives ◽  
Fungal Cell ◽  
Erythrocyte Lysis ◽  
Low Cytotoxicity ◽  
High Antifungal Activity

Abstract Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. Key points • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. Graphical abstract

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