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 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.

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.

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 The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in Aspergillus fumigatus

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Yuan Chen ◽  
Francois Le Mauff ◽  
Yan Wang ◽  
Ruiyang Lu ◽  
Donald C. Sheppard ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Aspergillus Fumigatus ◽  
Biofilm Formation ◽  
Wall Stress ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Content Type ◽  
Cell Wall Stress ◽  
Chitin Synthases

ABSTRACT Polysaccharides are key components of both the fungal cell wall and biofilm matrix. Despite having distinct assembly and regulation pathways, matrix exopolysaccharide and cell wall polysaccharides share common substrates and intermediates in their biosynthetic pathways. It is not clear, however, if the biosynthetic pathways governing the production of these polysaccharides are cooperatively regulated. Here, we demonstrate that cell wall stress promotes production of the exopolysaccharide galactosaminogalactan (GAG)-depend biofilm formation in the major fungal pathogen of humans Aspergillus fumigatus and that the transcription factor SomA plays a crucial role in mediating this process. A core set of SomA target genes were identified by transcriptome sequencing and chromatin immunoprecipitation coupled to sequencing (ChIP-Seq). We identified a novel SomA-binding site in the promoter regions of GAG biosynthetic genes agd3 and ega3, as well as its regulators medA and stuA. Strikingly, this SomA-binding site was also found in the upstream regions of genes encoding the cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Thus, SomA plays a direct regulation of both GAG and cell wall polysaccharide biosynthesis. Consistent with these findings, SomA is required for the maintenance of normal cell wall architecture and compositions in addition to its function in biofilm development. Moreover, SomA was found to globally regulate glucose uptake and utilization, as well as amino sugar and nucleotide sugar metabolism, which provides precursors for polysaccharide synthesis. Collectively, our work provides insight into fungal adaptive mechanisms in response to cell wall stress where biofilm formation and cell wall homeostasis were synchronously regulated. IMPORTANCE The cell wall is essential for fungal viability and is absent from human hosts; thus, drugs disrupting cell wall biosynthesis have gained more attention. Caspofungin is a member of a new class of clinically approved echinocandin drugs to treat invasive aspergillosis by blocking β-1,3-glucan synthase, thus damaging the fungal cell wall. Here, we demonstrate that caspofungin and other cell wall stressors can induce galactosaminogalactan (GAG)-dependent biofilm formation in the human pathogen Aspergillus fumigatus. We further identified SomA as a master transcription factor playing a dual role in both biofilm formation and cell wall homeostasis. SomA plays this dual role by direct binding to a conserved motif upstream of GAG biosynthetic genes and genes involved in cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Collectively, these findings reveal a transcriptional control pathway that integrates biofilm formation and cell wall homeostasis and suggest SomA as an attractive target for antifungal drug development.

scholarly journals A Review on Microorganisms-Derived Products as Potential Antimicrobial Agents

2021 ◽  
Author(s):  
Alka Rani ◽  
Khem Chand Saini ◽  
Felix Bast ◽  
Sunita Varjani ◽  
Sanjeet Mehariya ◽  
...  
Keyword(s):  
Cell Wall ◽  
Antimicrobial Peptides ◽  
Bioactive Compounds ◽  
Mode Of Action ◽  
Antimicrobial Agents ◽  
State Of The Art ◽  
Drug Resistant ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Streptomyces Sp

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and micro algae are the auspicious source of vital bioactive compounds. In this review, the existing state of the art re-garding antimicrobial molecules from microorganisms has been summarized. The potential an-timicrobial compounds from actinomycetes, particularly Streptomyces sp.; archaea; fungi including endophytic and marine-derived fungi, mushroom; yeast, and microalgae were briefly described. Furthermore, this review briefly summarized the activity and mode of action of bacteriocins, a ribosomally synthesized antimicrobial peptides product of Eurotium sp., Streptomyces parvulus, S. thermophiles, Lactococcus lactis, etc. Bacteriocins have inherent properties such as targeting multi-ple-drug resistant pathogens, which allows them to be considered next-generation antibiotics. Similarly, Glarea lozoyensis derived antifungal lipohexpeptides i.e., pneumocandins, inhibits 1,3-β-glucan synthase of the fungal cell wall and acts as a precursor for the synthesis of caspo-fungin, is also elaborated. In conclusion, this review highlights the possibility of using microor-ganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical ap-plications. However, more investigations are still required to separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

scholarly journals Coordination Between Fission Yeast Glucan Formation and Growth Requires a Sphingolipase Activity

Genetics ◽  
2001 ◽  
Vol 158 (4) ◽  
pp. 1397-1411 ◽  
Author(s):  
Anna Feoktistova ◽  
Paula Magnelli ◽  
Claudia Abeijon ◽  
Pilar Perez ◽  
Robert L Lester ◽  
...  
Keyword(s):  
Cell Wall ◽  
Secretory Pathway ◽  
Temperature Sensitive ◽  
Cell Wall Formation ◽  
Wild Type ◽  
Wall Formation ◽  
Biochemical Analyses ◽  
Membrane Spanning ◽  
Mutant Cells ◽  
Large Deposits

Abstractcss1 mutants display a novel defect in Schizosaccharomyces pombe cell wall formation. The mutant cells are temperature-sensitive and accumulate large deposits of material that stain with calcofluor and aniline blue in their periplasmic space. Biochemical analyses of this material indicate that it consists of α- and β-glucans in the same ratio as found in cell walls of wild-type S. pombe. Strikingly, the glucan deposits in css1 mutant cells do not affect their overall morphology. The cells remain rod shaped, and the thickness of their walls is unaltered. Css1p is an essential protein related to mammalian neutral sphingomyelinase and is responsible for the inositolphosphosphingolipid-phospholipase C activity observed in S. pombe membranes. Furthermore, expression of css1+ can compensate for loss of ISC1, the enzyme responsible for this activity in Saccharomyces cerevisiae membranes. Css1p localizes to the entire plasma membrane and secretory pathway; a C-terminal fragment of Css1p, predicted to encode a single membrane-spanning segment, is sufficient to direct membrane localization of the heterologous protein, GFP. Our results predict the existence of an enzyme(s) or process(es) essential for the coordination of S. pombe cell wall formation and division that is, in turn, regulated by a sphingolipid metabolite.

scholarly journals Drug Interaction Studies of a Glucan Synthase Inhibitor (LY 303366) and a Chitin Synthase Inhibitor (Nikkomycin Z) for Inhibition and Killing of Fungal Pathogens

2000 ◽  
Vol 44 (9) ◽  
pp. 2547-2548 ◽  
Author(s):  
David A. Stevens
Keyword(s):  
Cell Wall ◽  
Fungal Pathogens ◽  
Enzyme Inhibitors ◽  
Chitin Synthase ◽  
Synergistic Activity ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Nikkomycin Z ◽  
Synthase Inhibitor

ABSTRACT The interaction between inhibitors of components of the fungal cell wall, glucan and chitin, was studied in vitro with the respective synthase enzyme inhibitors LY 303366 and nikkomycin Z. WithAspergillus fumigatus synergy was noted for inhibition and killing, and synergistic activity was also noted for some isolates of other species presently regarded as difficult to treat.

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