Disruption of fungal cell wall by antifungal<i>Echinacea</i>extracts

Mir-Rashed, Nadereh; Cruz, Isabel B.; Jessulat, Matthew; Dumontier, Michel; Chesnais, Claire; Ng, Juliana; Amiguet, Virginie Treyvaud; Golshani, Ashkan; Arnason, John T.; Smith, Myron L.

doi:10.3109/13693781003767584

Cited by 24 publications

(24 citation statements)

References 40 publications

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“…The cell wall stressors utilized were Echinacea, calcofluor white, Congo red, and caffeine. Echinacea is a natural herb used as an antifungal treatment and is thought to target the fungal cell wall (60,76). Congo red binds to and disrupts the cell wall by inhibiting ␤-1,3-glucan assembly within the cell wall, and calcofluor white disrupts chitin synthesis and is able to bind chitin and inhibit the assembly of chitin fibrils within the cell wall (26,40,50,70,71).…”

Section: Resultsmentioning

confidence: 99%

Axl2 Integrates Polarity Establishment, Maintenance, and Environmental Stress Response in the Filamentous Fungus Ashbya gossypii

Anker

Gladfelter

2011

Eukaryot Cell

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In budding yeast, new sites of polarity are chosen with each cell cycle and polarization is transient. In filamentous fungi, sites of polarity persist for extended periods of growth and new polarity sites can be established while existing sites are maintained. How the polarity establishment machinery functions in these distinct growth forms found in fungi is still not well understood. We have examined the function of Axl2, a transmembrane bud site selection protein discovered in Saccharomyces cerevisiae, in the filamentous fungus Ashbya gossypii. A. gossypii does not divide by budding and instead exhibits persistent highly polarized growth, and multiple axes of polarity coexist in one cell. A. gossypii axl2⌬ (Agaxl2⌬) cells have wavy hyphae, bulbous tips, and a high frequency of branch initiations that fail to elongate, indicative of a polarity maintenance defect. Mutant colonies also have significantly lower radial growth and hyphal tip elongation speeds than wild-type colonies, and Agaxl2⌬ hyphae have depolarized actin patches. Consistent with a function in polarity, AgAxl2 localizes to hyphal tips, branches, and septin rings. Unlike S. cerevisiae Axl2, AgAxl2 contains a Mid2 homology domain and may function to sense or respond to environmental stress. In support of this idea, hyphae lacking AgAxl2 also display hypersensitivity to heat, osmotic, and cell wall stresses. Axl2 serves to integrate polarity establishment, polarity maintenance, and environmental stress response for optimal polarized growth in A. gossypii.The establishment and maintenance of cell polarity are essential for proper cell morphology and growth in both unicellular and multicellular eukaryotes (25, 39). Directional growth, neuronal development and function, membrane trafficking in epithelial cells, and whole-cell motility by chemotaxis all rely on the generation of cell polarity (5, 88, 97). Polar growth has been linked to fungal virulence in human pathogens such as Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, and Paracoccidioides brasiliensis (3,6,67,80). Many mechanisms governing cell polarity and polarized growth were discovered in the budding yeast, Saccharomyces cerevisiae, and are highly conserved from unicellular eukaryotes to humans (62).In S. cerevisiae, budding can occur in either an axial or a bipolar manner, which is determined by specific landmark proteins. The axial landmark consists of the septin complex, S. cerevisiae Bud3 (ScBud3), ScBud4, ScAxl1, and ScAxl2 and functions by recruiting members of the Cdc42 signaling pathway (1,14,30,31,38,44,45,69,72,98). The localization and activation of Cdc42 at sites specified by the landmarks then direct bud formation through polarization of the actin cytoskeleton (2, 99). Polarized actin cables form tracks on which myosins transport secretory vesicles to the growing bud (11,29,37). Polarized cortical actin patches are sites of endocytosis and as such can function to internalize any polarity factors that diffuse beyond the region of polarized growth (36,57,61).ScA...

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Section: Resultsmentioning

confidence: 99%

Axl2 Integrates Polarity Establishment, Maintenance, and Environmental Stress Response in the Filamentous Fungus Ashbya gossypii

Anker

Gladfelter

2011

Eukaryot Cell

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“…G418 and eugenol were purchased from Sigma-Aldrich (Oakville, ON, Canada). Ethanolic root extracts of Echinacea purpurea were used as a positive control in membrane disruption assays and prepared as described previously [15].…”

Section: Methodsmentioning

confidence: 99%

The Antifungal Eugenol Perturbs Dual Aromatic and Branched-Chain Amino Acid Permeases in the Cytoplasmic Membrane of Yeast

et al. 2013

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Eugenol is an aromatic component of clove oil that has therapeutic potential as an antifungal drug, although its mode of action and precise cellular target(s) remain ambiguous. To address this knowledge gap, a chemical-genetic profile analysis of eugenol was done using ∼4700 haploid Saccharomyces cerevisiae gene deletion mutants to reveal 21 deletion mutants with the greatest degree of susceptibility. Cellular roles of deleted genes in the most susceptible mutants indicate that the main targets for eugenol include pathways involved in biosynthesis and transport of aromatic and branched-chain amino acids. Follow-up analyses showed inhibitory effects of eugenol on amino acid permeases in the yeast cytoplasmic membrane. Furthermore, phenotypic suppression analysis revealed that eugenol interferes with two permeases, Tat1p and Gap1p, which are both involved in dual transport of aromatic and branched-chain amino acids through the yeast cytoplasmic membrane. Perturbation of cytoplasmic permeases represents a novel antifungal target and may explain previous observations that exposure to eugenol results in leakage of cell contents. Eugenol exposure may also contribute to amino acid starvation and thus holds promise as an anticancer therapeutic drug. Finally, this study provides further evidence of the usefulness of the yeast Gene Deletion Array approach in uncovering the mode of action of natural health products.

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“…The Echinacea sp extract inhibited 10 genes involved in cell wall integrity and structure of Saccharomyces cerevisiae and the fluorescence microscopy showed more susceptibility to cell wall damage (Mir‐Rashed et al . ).…”

Section: Resultsmentioning

confidence: 97%

Growth inhibition and antioxidative response of wood decay fungi exposed to plant extracts ofCaseariaspecies

Bento

Torres

Fialho

et al. 2013

Lett Appl Microbiol

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Significance and Impact of the Study: The Casearia plant extracts exhibited important antifungal activity on wood decay fungi and triggered oxidative stress process, an inhibitory mechanism rarely studied in filamentous fungi exposed to plant extracts. Therefore, a starting point was provided for the development of natural compounds-based products as an alternative to chemical fungicides. In addition, subsidies were given to further studies in order to elucidate in more detail how compounds present in extracts of native tropical plants affect the physiology of fungi. AbstractLigninolytic fungi take part in critical processes in ecosystems such as nutrient recycling; however, some fungal species can be pathogenic to forest and urban trees and deteriorate wood products. The tropical flora is an important source of antimicrobial compounds environmentally safer than traditional wood preservatives. Therefore, this study aimed to evaluate the inhibitory activity of ethanol plant extracts of Casearia sylvestris and Casearia decandra on the white-rot wood decay basidiomycetes Trametes villosa and Pycnoporus sanguineus. In addition, the effect of the extracts on the fungal antioxidative metabolism was studied. Among the different substances present in the extracts, the phytochemical analyses identified a clerodane diterpenoid (C. sylvestris) and cinnamic acid, hydroquinone and b-sitosterol (C. decandra). The extracts inhibited the fungi up to 70% and caused hyphal morphology changes. The extracts triggered oxidative stress process as indicated by the increased levels of the antioxidant enzymes catalase and glutathione reductase. Therefore, the Casearia extracts are a potential source of natural biocides to control wood decay fungi, and one of the mechanisms of action is the oxidative stress.

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Disruption of fungal cell wall by antifungalEchinaceaextracts

Cited by 24 publications

References 40 publications

Axl2 Integrates Polarity Establishment, Maintenance, and Environmental Stress Response in the Filamentous Fungus Ashbya gossypii

Axl2 Integrates Polarity Establishment, Maintenance, and Environmental Stress Response in the Filamentous Fungus Ashbya gossypii

The Antifungal Eugenol Perturbs Dual Aromatic and Branched-Chain Amino Acid Permeases in the Cytoplasmic Membrane of Yeast

Growth inhibition and antioxidative response of wood decay fungi exposed to plant extracts ofCaseariaspecies

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