The differences between fungal α-glucan synthase determining pullulan synthesis and that controlling cell wall α-1,3 glucan synthesis

2020 ◽  
Vol 162 ◽  
pp. 436-444 ◽  
Author(s):  
Cong-Yan Qi ◽  
Shu-Lei Jia ◽  
Xin Wei ◽  
Guang Yang ◽  
Zhe Chi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Glucan Synthase ◽  
Glucan Synthesis

scholarly journals Identification of a putative alpha-glucan synthase essential for cell wall construction and morphogenesis in fission yeast

1998 ◽  
Vol 95 (16) ◽  
pp. 9161-9166 ◽  
Author(s):  
Frans Hochstenbach ◽  
Frans M. Klis ◽  
Herman van den Ende ◽  
Elly van Donselaar ◽  
Peter J. Peters ◽  
...  
Keyword(s):  
Cell Wall ◽  
Fission Yeast ◽  
Transmembrane Domain ◽  
Temperature Sensitive ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Catalytic Domains ◽  
Carbohydrate Polymer ◽  
Glucan Synthesis ◽  
Mutant Cells

The cell wall protects fungi against lysis and determines their cell shape. Alpha-glucan is a major carbohydrate component of the fungal cell wall, but its function is unknown and its synthase has remained elusive. Here, we describe a fission yeast gene,ags1+, which encodes a putative alpha-glucan synthase. In contrast to the structure of other carbohydrate polymer synthases, the predicted Ags1 protein consists of two probable catalytic domains for alpha-glucan assembly, namely an intracellular domain for alpha-glucan synthesis and an extracellular domain speculated to cross-link or remodel alpha-glucan. In addition, the predicted Ags1 protein contains a multipass transmembrane domain that might contribute to transport of alpha-glucan across the membrane. Loss of Ags1p function in a temperature-sensitive mutant results in cell lysis, whereas mutant cells grown at the semipermissive temperature contain decreased levels of cell wall alpha-glucan and fail to maintain rod shapes, causing rounding of the cells. These findings demonstrate that alpha-glucan is essential for fission yeast morphogenesis.

scholarly journals Cellular Accumulation, Localization, and Activity of a Synthetic Cyclopeptamine in Fungi

1998 ◽  
Vol 42 (2) ◽  
pp. 389-393 ◽  
Author(s):  
John O. Capobianco ◽  
Dorothy Zakula ◽  
David J. Frost ◽  
Robert C. Goldman ◽  
Leping Li ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Glucan Synthase ◽  
Cellular Accumulation ◽  
Drug Concentrations ◽  
Drug Reservoir ◽  
Membrane Bound ◽  
Glucan Synthesis ◽  
Major Drug

ABSTRACT A novel synthetic cyclopeptamine, A172013, rapidly accumulated by passive diffusion into Candida albicans CCH442. Drug influx could not be totally facilitated by the membrane-bound target, β-(1,3)-glucan synthase, since accumulation was unsaturable at drug concentrations up to 10 μg/ml (about 1.6 × 10−7molecules/cell), or 25× MIC. About 55 and 23% of the cell-incorporated drug was associated with the cell wall and protoplasts, respectively. Isolated microsomes contained 95% of the protoplast-associated drug, which was fully active against glucan synthesis in vitro. Drug (0.1 μg/ml) accumulation was rapid and complete after 5 min in several fungi tested, including a lipopeptide/cyclopeptamine-resistant strain of C. albicans(LP3-1). The compound penetrated to comparable levels in both yeast and hyphal forms of C. albicans, and accumulation inAspergillus niger was 20% that in C. albicans. These data indicated that drug-cell interactions were driven by the amphiphilic nature of the compound and that the cell wall served as a major drug reservoir.

Recent Status and Advancements in the Development of Antifungal Agents: Highlights on Plant and Marine Based Antifungals

2019 ◽  
Vol 19 (10) ◽  
pp. 812-830 ◽  
Author(s):  
P. Marie Arockianathan ◽  
Monika Mishra ◽  
Rituraj Niranjan
Keyword(s):  
Cell Wall ◽  
Antifungal Agents ◽  
Fungal Diseases ◽  
Fungal Cell Wall ◽  
Fungal Resistance ◽  
Ergosterol Biosynthesis ◽  
Fungal Cell ◽  
Ergosterol Synthesis ◽  
Glucan Synthesis ◽  
Anti Fungal

The developing resistance in fungi has become a key challenge, which is being faced nowadays with the available antifungal agents in the market. Further search for novel compounds from different sources has been explored to meet this problem. The current review describes and highlights recent advancement in the antifungal drug aspects from plant and marine based sources. The current available antifungal agents act on specific targets on the fungal cell wall, like ergosterol synthesis, chitin biosynthesis, sphingolipid synthesis, glucan synthesis etc. We discuss some of the important anti-fungal agents like azole, polyene and allylamine classes that inhibit the ergosterol biosynthesis. Echinocandins inhibit β-1, 3 glucan synthesis in the fungal cell wall. The antifungals poloxins and nikkomycins inhibit fungal cell wall component chitin. Apart from these classes of drugs, several combinatorial therapies have been carried out to treat diseases due to fungal resistance. Recently, many antifungal agents derived from plant and marine sources showed potent activity. The renewed interest in plant and marine derived compounds for the fungal diseases created a new way to treat these resistant strains which are evident from the numerous literature publications in the recent years. Moreover, the compounds derived from both plant and marine sources showed promising results against fungal diseases. Altogether, this review article discusses the current antifungal agents and highlights the plant and marine based compounds as a potential promising antifungal agents.

scholarly journals Genomic Approach to Identification of Mutations Affecting Caspofungin Susceptibility in Saccharomyces cerevisiae

2004 ◽  
Vol 48 (10) ◽  
pp. 3871-3876 ◽  
Author(s):  
Sarit Markovich ◽  
Aya Yekutiel ◽  
Itamar Shalit ◽  
Yona Shadkchan ◽  
Nir Osherov
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Ergosterol Biosynthesis ◽  
Membrane Function ◽  
Minimum Effective Concentration ◽  
Fourfold Increase ◽  
Microdilution Method ◽  
New Genes ◽  
Broth Microdilution Method ◽  
Glucan Synthesis

ABSTRACT The antifungal agent caspofungin (CAS) specifically interferes with glucan synthesis and cell wall formation. To further study the cellular processes affected by CAS, we analyzed a Saccharomyces cerevisiae mutant collection (4,787 individual knockout mutations) to identify new genes affecting susceptibility to the drug. This collection was screened for increased CAS sensitivity (CAS-IS) or increased CAS resistance (CAS-IR). MICs were determined by the broth microdilution method. Disruption of 20 genes led to CAS-IS (four- to eightfold reductions in the MIC). Eleven of the 20 genes are involved in cell wall and membrane function, notably in the protein kinase C (PKC) integrity pathway (MID2, FKS1, SMI1, and BCK1), chitin and mannan biosynthesis (CHS3, CHS4, CHS7, and MNN10), and ergosterol biosynthesis (ERG5 and ERG6). Four of the 20 genes (TPO1, VPS65, VPS25, and CHC1) are involved in vacuole and transport functions, 3 of the 20 genes (CCR4, POP2, and NPL3) are involved in the control of transcription, and 2 of the 20 genes are of unknown function. Disruption of nine additional genes led to CAS-IR (a fourfold increase of MIC). Five of these nine genes (SLG1, ERG3, VRP1, CSG2, and CKA2) are involved in cell wall function and signal transduction, and two of the nine genes (VPS67 and SAC2) are involved in vacuole function. To assess the specificity of susceptibility to CAS, the MICs of amphotericin B, fluconazole, flucytosine, and calcofluor for the strains were tested. Seven of 20 CAS-IS strains (with disruption of FKS1, SMI1, BCK1, CHS4, ERG5, TPO1, and ILM1) and 1 of 9 CAS-IR strains (with disruption of SLG1) demonstrated selective susceptibility to CAS. To further explore the importance of PKC in CAS susceptibility, the activity of the PKC inhibitor staurosporine in combination with CAS was tested against eight Aspergillus clinical isolates by the microdilution assay. Synergistic or synergistic-to-additive activities were found against all eight isolates by use of both MIC and minimum effective concentration endpoints.

The yeast KRE5 gene encodes a probable endoplasmic reticulum protein required for (1----6)-beta-D-glucan synthesis and normal cell growth

1990 ◽  
Vol 10 (6) ◽  
pp. 3013-3019
Author(s):  
P Meaden ◽  
K Hill ◽  
J Wagner ◽  
D Slipetz ◽  
S S Sommer ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Wall ◽  
Cell Growth ◽  
Normal Cell ◽  
Secretory Pathway ◽  
Endoplasmic Reticulum Retention Signal ◽  
Endoplasmic Reticulum Protein ◽  
Glucan Synthesis ◽  
Retention Signal ◽  
Sequential Assembly

Yeast kre mutants define a pathway of cell wall (1----6)-beta-D-glucan synthesis, and mutants in genes KRE5 and KRE6 appear to interact early in such a pathway. We have cloned KRE5, and the sequence predicts the product to be a large, hydrophilic, secretory glycoprotein which contains the COOH-terminal endoplasmic reticulum retention signal, HDEL. Deletion of the KRE5 gene resulted in cells with aberrant morphology and extremely compromised growth. Suppressors to the KRE5 deletions arose at a frequency of 1 in 10(7) to 1 in 10(8) and permitted an analysis of deletions which were found to contain no alkali-insoluble (1----6)-beta-D-glucan. These results indicate a role for (1----6)-beta-D-glucan in normal cell growth and suggest a model for sequential assembly of (1----6)-beta-D-glucan in the yeast secretory pathway.

Localisation of the Schizosaccharomyces pombe rho1p GTPase and its involvement in the organisation of the actin cytoskeleton

1997 ◽  
Vol 110 (20) ◽  
pp. 2547-2555 ◽  
Author(s):  
M. Arellano ◽  
A. Duran ◽  
P. Perez
Keyword(s):  
Cell Wall ◽  
Actin Cytoskeleton ◽  
Schizosaccharomyces Pombe ◽  
Antifungal Drugs ◽  
Dominant Negative ◽  
Cortical Actin ◽  
Glucan Synthase ◽  
Cell Wall Growth ◽  
Wall Growth ◽  
Mutant Cells

The Schizosaccharomyces pombe rho1p GTPase directly activates the (1–3) beta-D-glucan synthase and participates in the regulation of cell wall growth and morphogenesis in this fission yeast. Indirect immunofluorescence experiments using rho1p tagged with hemagglutinin have revealed that rho1p was located at the growing tips during interphase and at the septum prior to cytokinesis, localising to the same areas as actin patches. In S. pombe cdc10-129 mutant cells, arrested in G1, HA-rho1p accumulates at one tip whereas in cdc25-22 mutants, arrested in G2, HA-rho1p accumulates at both tips. In tea1-1 and tea2-1 cdc11-119 mutant cells, HA-rho1p is localised to the new growing tips. Overexpression of different rho1 mutant alleles caused different effects on cortical actin patch distribution, (1–3) beta-D-glucan synthase activation, and sensitivity to cell wall specific antifungal drugs. These results indicate that multiple cellular components are activated by rho1p. Overexpression of the dominant negative rho1T20N allele was lethal as was the rho1+ deletion. Moreover, when rho1+ expression was repressed in actively growing S. pombe, cells died in about 10 to 12 hours. Under these conditions, normal cell morphology was maintained but the level of (1–3) beta-D-glucan synthase activity decreased and the actin patches disappeared. Most cells lysed after cytokinesis during the process of separation, and lysis was not prevented by an osmotic stabiliser. We conclude that rho1p localisation is restricted to growth areas and regulated during the cell cycle and that rho1p is involved in cell wall growth and actin cytoskeleton organisation in S. pombe.

scholarly journals Length Specificity and Polymerization Mechanism of (1,3)-β-d-Glucan Synthase in Fungal Cell Wall Biosynthesis

Biochemistry ◽  
2020 ◽  
Vol 59 (5) ◽  
pp. 682-693 ◽  
Author(s):  
Abhishek Chhetri ◽  
Anna Loksztejn ◽  
Hai Nguyen ◽  
Kaila M. Pianalto ◽  
Mi Jung Kim ◽  
...  
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Cell Wall Biosynthesis ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Polymerization Mechanism

scholarly journals Yeast Mycocins: a great potential for application in health

2020 ◽  
Vol 20 (3) ◽  
Author(s):  
Bruna L Nascimento ◽  
Mateus F Delabeneta ◽  
Lana Rubia B Rosseto ◽  
Daniele S B Junges ◽  
Ana Paula Paris ◽  
...  
Keyword(s):  
Cell Wall ◽  
Clinical Practice ◽  
Mechanism Of Action ◽  
Extracellular Proteins ◽  
Main Mechanism ◽  
Minimal Toxicity ◽  
Glucan Synthesis ◽  
Epidemiological Markers

ABSTRACT Mycocins have demonstrated inhibition of fungi, bacteria, parasites and viruses, in addition to being studied as epidemiological markers and in the development of vaccines. They are defined as extracellular proteins or glycoproteins with different activities, the main mechanism of action being the inhibition of β-glucan synthesis in the cell wall of sensitive strains. Given the resistance problems created by several microorganisms to agents commonly used in clinical practice, the discovery of new substances with this purpose becomes essential. Mycocins have potential as anti-microbials because they show minimal toxicity and do not present resistance.

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