scholarly journals Structure, Cellular Distribution, Antigenicity, and Biological Functions of Fonsecaea pedrosoi Ceramide Monohexosides

2005 ◽  
Vol 73 (12) ◽  
pp. 7860-7868 ◽  
Author(s):  
Leonardo Nimrichter ◽  
Mariana D. Cerqueira ◽  
Eduardo A. Leitão ◽  
Kildare Miranda ◽  
Ernesto S. Nakayasu ◽  
...  
Keyword(s):  
Cell Wall ◽  
Structural Difference ◽  
Structural Diversity ◽  
Fungal Species ◽  
Hydroxyl Group ◽  
Current Evidence ◽  
Fonsecaea Pedrosoi ◽  
Fungal Cell ◽  
Long Chain Base ◽  
Antifungal Action

ABSTRACT Monohexosylceramides (CMHs, or cerebrosides) have been reported as membrane and cell wall constituents of both pathogenic and nonpathogenic fungi, presenting remarkable differences in their ceramide moiety compared to mammalian CMHs. Current evidence suggests that CMHs are involved in fungal differentiation and growth and contribute to host immune response. Here we describe a structural diversity between cerebrosides obtained from different forms of the human pathogen Fonsecaea pedrosoi. The major CMH species produced by conidial forms displayed the same structure previously demonstrated by our group for mycelia, an N-2′-hydroxyhexadecanoyl-1-β-d-glucopyranosyl-9-methyl-4,8-sphingadienine. However, the major cerebroside species purified from sclerotic cells carries an additional hydroxyl group, bound to its long-chain base. The structural difference between cerebrosides from mycelial and sclerotic cells was apparently not relevant for their antigenicity, since they were both recognized at similar levels by sera from individuals with chromoblastomycosis and a monoclonal antibody to a conserved cerebroside structure. Preincubation of fungal cells with anti-CMH monoclonal antibodies had no effect on the interaction of F. pedrosoi sclerotic cells with murine macrophages. In contrast to what has been described for other fungal species, sclerotic bodies are resistant to the antifungal action of anti-CMH antibodies. Immunofluorescence analysis showed that recognition of sclerotic cells by these antibodies only occurs at cell wall regions in which melanization is not evident. Accordingly, melanin removal with alkali results in an increased reaction of fungal cells with anti-CMH antibodies. Our results indicate that cerebroside expression in F. pedrosoi cells is associated with dimorphism and melanin assembly on the fungal cell wall.

scholarly journals Spatial Distribution of a Porphyrin-Based Photosensitizer Reveals Mechanism of Photodynamic Inactivation of Candida albicans

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Voit ◽  
Fabian Cieplik ◽  
Johannes Regensburger ◽  
Karl-Anton Hiller ◽  
Anita Gollmer ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Cell Envelope ◽  
Antimicrobial Photodynamic Therapy ◽  
Fungal Cell ◽  
Before And After ◽  
Antifungal Action ◽  
Complete Cell ◽  
Further Development

The antimicrobial photodynamic therapy (aPDT) is a promising approach for the control of microbial and especially fungal infections such as mucosal mycosis. TMPyP [5,10,15, 20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate] is an effective photosensitizer (PS) that is commonly used in aPDT. The aim of this study was to examine the localization of TMPyP in Candida albicans before and after irradiation with visible light to get information about the cellular mechanism of antifungal action of the photodynamic process using this PS. Immediately after incubation of C. albicans with TMPyP, fluorescence microscopy revealed an accumulation of the PS in the cell envelope. After irradiation with blue light the complete cell showed red fluorescence, which indicates, that aPDT is leading to a damage in the cell wall with following influx of PS into the cytosol. Incubation of C. albicans with Wheat Germ Agglutinin (WGA) could confirm the cell wall as primary binding site of TMPyP. The finding that the porphyrin accumulates in the fungal cell wall and does not enter the interior of the cell before irradiation makes it unlikely that resistances can emerge upon aPDT. The results of this study may help in further development and modification of PS in order to increase efficacy against fungal infections such as those caused by C. albicans.

scholarly journals The Antifungal Action Mode of N-Phenacyldibromobenzimidazoles

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5463
Author(s):  
Monika Staniszewska ◽  
Łukasz Kuryk ◽  
Aleksander Gryciuk ◽  
Joanna Kawalec ◽  
Marta Rogalska ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
Cell Membrane ◽  
Chitinolytic Activity ◽  
Irreversible Damage ◽  
Fungal Cell ◽  
Action Mode ◽  
Structure Activity ◽  
Dependent Inhibition ◽  
Antifungal Action

Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure–activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobenzimidazole analogues (5e–f and 5h). The substitution of chlorine atoms to the benzene ring of the N-phenacyl substituent extended the anti-C. albicans action (5e with 2,4-Cl2 or 5f with 3,4-Cl2). The excellent results for N-phenacyldibromobenzimidazole 5h against the C. albicans reference and clinical isolate showed IC50 = 8 µg/mL and %I = 100 ± 3, respectively. Compound 5h was fungicidal against the C. neoformans isolate. Compound 5h at 160–4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of 5h, in accordance with the patterns observed for the following substrates: 4-nitrophenyl-N-acetyl-β-d-glucosaminide and 4-nitrophenyl-β-d-N,N′,N″-triacetylchitothiose. Derivative 5h at 16 µg/mL: (1) it affected cell wall by inducing β-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the C. albicans biofilm-treated. Compound 5h exerted Candida-dependent inhibition of virulence factors.

scholarly journals Unconventional Constituents and Shared Molecular Architecture of the Melanized Cell Wall of C. neoformans and Spore Wall of S. cerevisiae

2020 ◽  
Vol 6 (4) ◽  
pp. 329
Author(s):  
Christine Chrissian ◽  
Coney Pei-Chen Lin ◽  
Emma Camacho ◽  
Arturo Casadevall ◽  
Aaron M. Neiman ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Building Blocks ◽  
Cell Types ◽  
Resistant Cell ◽  
Spore Wall ◽  
Fungal Species ◽  
Resonance Spectroscopy ◽  
Molecular Architecture ◽  
Fungal Cell

The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from Saccharomyces cerevisiae spores and Cryptococcus neoformans melanized cells. The specialized cell walls of these two divergent fungi are highly similar in composition. Both use chitosan, the deacetylated derivative of chitin, as a scaffold on which a polyaromatic polymer, dityrosine and melanin, respectively, is assembled. Additionally, we demonstrate that a previously identified but uncharacterized component of the S. cerevisiae spore wall is composed of triglycerides, which are also present in the C. neoformans melanized cell wall. Moreover, we identify a tyrosine-derived constituent in the C. neoformans wall that, although it is not dityrosine, is a non-pigment constituent of the cell wall. The similar composition of the walls of these two phylogenetically distant species suggests that triglycerides, polyaromatics, and chitosan are basic building blocks used to assemble highly stress-resistant cell walls and the use of these constituents may be broadly conserved in other fungal species.

scholarly journals Spatial mapping of immunological epitopes in the Candida cell wall using C-type lectin probes

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Ingrida Vendele ◽  
Ten Feizi ◽  
Maria Spyrou ◽  
Mark Stappers ◽  
Gordon Brown ◽  
...  
Keyword(s):  
Cell Wall ◽  
Three Dimensional ◽  
Fungal Species ◽  
Physiological Adaptation ◽  
Dimensional Structure ◽  
Immune Reactivity ◽  
Fungal Cell ◽  
Lectin Receptor ◽  
Composition Changes

The primary recognition event between a fungal pathogen and the immune system normally involves the engagement of a pattern recognition receptor with specific components of the cell wall. However, the cell wall is a complex three dimensional structure whose composition changes rapidly in accordance with environmental stimuli. Therefore it is important to know what is the precise nature of the primary recognition event, how many events occur to activate the immune response and how these recognition events are affected by changes in cell wall architecture, cellular morphogenesis and physiological adaptation of the pathogen to specific niches in the human body. We address this fundamental question using four soluble immune C-Type lectin receptor-probes which recognize specific mannans and β-1,3 glucan in the cell wall. We use these C-type lectin probes to demonstrate that mannan epitopes are differentially distributed in the inner and outer layers of fungal cell wall in a clustered or diffuse manner. Immune reactivity of fungal cell surfaces did not correlate with relatedness of different fungal species, and mannan-detecting receptor-probes discriminated between cell surface mannans generated by the same fungus growing under different conditions. These studies demonstrate that mannan-epitopes within fungal cell walls are differentially distributed and dynamically expressed as the fungus adapted to microenvironments that would be encountered in vivo.

scholarly journals Unravelling the enigmatic origin of calcitic nanofibres in soils and caves: purely physicochemical or biogenic processes?

2014 ◽  
Vol 11 (1) ◽  
pp. 975-1019
Author(s):  
S. Bindschedler ◽  
G. Cailleau ◽  
O. Braissant ◽  
L. Millière ◽  
D. Job ◽  
...  
Keyword(s):  
Cell Wall ◽  
Current Knowledge ◽  
Enzymatic Digestion ◽  
Global Scale ◽  
Fungal Species ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Widespread Occurrence ◽  
Terrestrial Environments ◽  
New Hypothesis

Abstract. Calcitic nanofibres are ubiquitous habits of secondary calcium carbonate (CaCO3) accumulations observed in calcareous vadose environments. Despite their widespread occurrence, the origin of these nanofeatures remains enigmatic. Three possible mechanisms fuel the debate: (i) purely physicochemical processes, (ii) mineralization of rod-shaped bacteria, and (iii) crystal precipitation on organic templates. Nanofibres can be either mineral (calcitic) or organic in nature. They are very often observed in association with Needle Fibre Calcite (NFC), another typical secondary CaCO3 habit in terrestrial environments. This association has contributed to some confusion between both habits, however they are truly two distinct calcitic features and their recurrent association is likely to be an important fact to help understanding the origin of nanofibres. In this manuscript the different hypotheses that currently exist to explain the origin of calcitic nanofibres are critically reviewed. In addition to this, a new hypothesis for the origin of nanofibres is proposed based on the fact that current knowledge attributes a fungal origin to NFC. As this feature and nanofibres are recurrently observed together, a possible fungal origin for nanofibres which are associated with NFC is investigated. Sequential enzymatic digestion of the fungal cell wall of selected fungal species demonstrates that the fungal cell wall can be a source of organic nanofibres. The obtained organic nanofibres show a striking morphological resemblance when compared to their natural counterparts, emphasizing a fungal origin for part of the organic nanofibres observed in association with NFC. It is further hypothesized that these organic nanofibres may act as templates for calcite nucleation in a biologically-influenced mineralization process, generating calcitic nanofibres. This highlights the possible involvement of Fungi in CaCO3 biomineralization processes, a role still poorly documented at present-day. Moreover, on a global scale, the organomineralization of organic nanofibres into calcitic nanofibres might have a great, however overlooked, impact on the biogeochemical cycles of both Ca and C.

scholarly journals Unravelling the enigmatic origin of calcitic nanofibres in soils and caves: purely physicochemical or biogenic processes?

2014 ◽  
Vol 11 (10) ◽  
pp. 2809-2825 ◽  
Author(s):  
S. Bindschedler ◽  
G. Cailleau ◽  
O. Braissant ◽  
L. Millière ◽  
D. Job ◽  
...  
Keyword(s):  
Cell Wall ◽  
Current Knowledge ◽  
Enzymatic Digestion ◽  
Global Scale ◽  
Fungal Species ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Widespread Occurrence ◽  
Terrestrial Environments ◽  
New Hypothesis

Abstract. Calcitic nanofibres are ubiquitous habits of secondary calcium carbonate (CaCO3) accumulations observed in calcareous vadose environments. Despite their widespread occurrence, the origin of these nanofeatures remains enigmatic. Three possible mechanisms fuel the debate: (i) purely physicochemical processes, (ii) mineralization of rod-shaped bacteria, and (iii) crystal precipitation on organic templates. Nanofibres can be either mineral (calcitic) or organic in nature. They are very often observed in association with needle fibre calcite (NFC), another typical secondary CaCO3 habit in terrestrial environments. This association has contributed to some confusion between both habits, however they are truly two distinct calcitic features and their recurrent association is likely to be an important fact to help understanding the origin of nanofibres. In this paper the different hypotheses that currently exist to explain the origin of calcitic nanofibres are critically reviewed. In addition to this, a new hypothesis for the origin of nanofibres is proposed based on the fact that current knowledge attributes a fungal origin to NFC. As this feature and nanofibres are recurrently observed together, a possible fungal origin for nanofibres which are associated with NFC is investigated. Sequential enzymatic digestion of the fungal cell wall of selected fungal species demonstrates that the fungal cell wall can be a source of organic nanofibres. The obtained organic nanofibres show a striking morphological resemblance when compared to their natural counterparts, emphasizing a fungal origin for part of the organic nanofibres observed in association with NFC. It is further hypothesized that these organic nanofibres may act as templates for calcite nucleation in a biologically influenced mineralization process, generating calcitic nanofibres. This highlights the possible involvement of fungi in CaCO3 biomineralization processes, a role still poorly documented. Moreover, on a global scale, the organomineralization of organic nanofibres into calcitic nanofibres might be an overlooked process deserving more attention to specify its impact on the biogeochemical cycles of both Ca and C.

scholarly journals Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls

2019 ◽  
Author(s):  
Ingrida Vendele ◽  
Janet A. Willment ◽  
Lisete M. Silva ◽  
Angelina S. Palma ◽  
Wengang Chai ◽  
...  
Keyword(s):  
Cell Wall ◽  
Immune Responses ◽  
Cell Walls ◽  
Fungal Pathogens ◽  
Fungal Species ◽  
Fungal Cell Wall ◽  
Immune Recognition ◽  
Cell Surfaces ◽  
Fungal Cell ◽  
Wall Components

AbstractDuring the course of fungal infection, pathogen recognition by the innate immune system is critical to initiate efficient protective immune responses. The primary event that triggers immune responses is the binding of Pattern Recognition Receptors (PRRs), which are expressed at the surface of host immune cells, to Pathogen-Associated Molecular Patterns (PAMPs) located predominantly in the fungal cell wall. Most fungi have mannosylated PAMPs in their cell walls and these are recognized by a range of C-type lectin receptors (CTLs). However, the precise spatial distribution of the ligands that induce immune responses within the cell walls of fungi are not well defined. We used recombinant IgG Fc-CTLs fusions of three murine mannan detecting CTLs, including dectin-2, the mannose receptor (MR) carbohydrate recognition domains (CRDs) 4-7 (CRD4-7), and human DC-SIGN (hDC-SIGN) and the β-1,3 glucan-binding lectin dectin-1 to map PRR ligands in the fungal cell wall. We show that epitopes of mannan-specific CTL receptors can be clustered or diffuse, superficial or buried in the inner cell wall. We demonstrate that PRR ligands do not correlate well with phylogenetic relationships between fungi, and that Fc-lectin binding discriminated between mannosides expressed on different cell morphologies of the same fungus. We also demonstrate CTL epitope differentiation during different phases of the growth cycle ofCandida albicansand that MR and DC-SIGN labelled outer chainN-mannans whilst dectin-2 labelled coreN-mannans displayed deeper in the cell wall. These immune receptor maps of fungal walls therefore reveal remarkable spatial, temporal and chemical diversity, indicating that the triggering of immune recognition events originates from multiple physical origins at the fungal cell surface.Author SummaryInvasive fungal infections remain an important health problem in immunocompromised patients. Immune recognition of fungal pathogens involves binding of specific cell wall components by pathogen recognition receptors (PRRs) and subsequent activation of immune defences. Some cell wall components are conserved among fungal species while other components are species-specific and phenotypically diverse. The fungal cell wall is dynamic and capable of changing its composition and organization when adapting to different growth niches and environmental stresses. Differences in the composition of the cell wall lead to differential immune recognition by the host. Understanding how changes in the cell wall composition affect recognition by PRRs is likely to be of major diagnostic and clinical relevance. Here we address this fundamental question using four soluble immune receptor-probes which recognize mannans and β-glucan in the cell wall. We use this novel methodology to demonstrate that mannan epitopes are differentially distributed in the inner and outer layers of fungal cell wall in a clustered or diffuse manner. Immune reactivity of fungal cell surfaces did not correlate with relatedness of different fungal species, and mannan-detecting receptor-probes discriminated between cell surface mannans generated by the same fungus growing under different conditions. These studies demonstrate that mannan-epitopes on fungal cell surfaces are differentially distributed within and between the cell walls of fungal pathogens.

scholarly journals A Glucan Synthase FKS1 Homolog inCryptococcus neoformans Is Single Copy and Encodes an Essential Function

1999 ◽  
Vol 181 (2) ◽  
pp. 444-453 ◽  
Author(s):  
John R. Thompson ◽  
Cameron M. Douglas ◽  
Weili Li ◽  
Chong K. Jue ◽  
Barnali Pramanik ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Single Copy ◽  
Fungal Species ◽  
Term Treatment ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Long Term Treatment

ABSTRACT Cryptococcal meningitis is a fungal infection, caused byCryptococcus neoformans, which is prevalent in immunocompromised patient populations. Treatment failures of this disease are emerging in the clinic, usually associated with long-term treatment with existing antifungal agents. The fungal cell wall is an attractive target for drug therapy because the syntheses of cell wall glucan and chitin are processes that are absent in mammalian cells. Echinocandins comprise a class of lipopeptide compounds known to inhibit 1,3-β-glucan synthesis, and at least two compounds belonging to this class are currently in clinical trials as therapy for life-threatening fungal infections. Studies ofSaccharomyces cerevisiae and Candida albicansmutants identify the membrane-spanning subunit of glucan synthase, encoded by the FKS genes, as the molecular target of echinocandins. In vitro, the echinocandins show potent antifungal activity against Candida and Aspergillusspecies but are much less potent against C. neoformans. In order to examine why C. neoformans cells are less susceptible to echinocandin treatment, we have cloned a homolog of S. cerevisiae FKS1 from C. neoformans. We have developed a generalized method to evaluate the essentiality of genes inCryptococcus and applied it to the FKS1 gene. The method relies on homologous integrative transformation with a plasmid that can integrate in two orientations, only one of which will disrupt the target gene function. The results of this analysis suggest that the C. neoformans FKS1 gene is essential for viability. The C. neoformans FKS1 sequence is closely related to the FKS1 sequences from other fungal species and appears to be single copy in C. neoformans. Furthermore, amino acid residues known to be critical for echinocandin susceptibility in Saccharomyces are conserved in theC. neoformans FKS1 sequence.

scholarly journals Glycobiology of Human Fungal Pathogens: New Avenues for Drug Development

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1348 ◽  
Author(s):  
Danielle J. Lee ◽  
Holly O’Donnell ◽  
Françoise H. Routier ◽  
Joe Tiralongo ◽  
Thomas Haselhorst
Keyword(s):  
Cell Wall ◽  
Immune System ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Treatment Options ◽  
Fungal Spores ◽  
Fungal Species ◽  
Cell Wall Polysaccharides ◽  
Fungal Cell ◽  
Sugar Transporters

Invasive fungal infections (IFI) are an increasing threat to the developing world, with fungal spores being ubiquitous and inhaled every day. Some fungal species are commensal organisms that are part of the normal human microbiota, and, as such, do not pose a threat to the immune system. However, when the natural balance of this association is disturbed or the host’s immune system is compromised, these fungal pathogens overtake the organism, and cause IFI. To understand the invasiveness of these pathogens and to address the growing problem of IFI, it is essential to identify the cellular processes of the invading organism and their virulence. In this review, we will discuss the prevalence and current options available to treat IFI, including recent reports of drug resistance. Nevertheless, the main focus of this review is to describe the glycobiology of human fungal pathogens and how various components of the fungal cell wall, particularly cell wall polysaccharides and glycoconjugates, are involved in fungal pathogenicity, their biosynthesis and how they can be potentially exploited to develop novel antifungal treatment options. We will specifically describe the nucleotide sugar transporters (NSTs) that are important in fungal survival and suggest that the inhibition of fungal NSTs may potentially be useful to prevent the establishment of fungal infections.

The Biology of Fungi

2019 ◽  
Author(s):  
Stephanie J. Smith ◽  
Rohini J. Manuel
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Wall ◽  
Germ Tube ◽  
Fungal Species ◽  
Molecular Techniques ◽  
Fungal Cell ◽  
Tube Test ◽  
Membrane Bound ◽  
Filamentous Material ◽  
One Fungus One Name

Fungi are found ubiquitously in the environment such as soil, water, and food. There are an estimated 1.5 million fungal species worldwide, although this number is felt to be grossly underestimated and is regularly updated. Of these vast numbers, around 500 fungi to date have been implicated in human disease. As opposed to bacteria, which are prokaryotes, fungi are eukaryotes, meaning they have a well-defined nucleus and have membrane- bound organelles in the cytoplasm, including an endoplasmic reticulum and a golgi apparatus. In 1969, the scientist R. H. Whittaker first proposed that organisms be classified into five kingdoms: Monera (Bacteria), Protista (Algae and Protozoans), Plantae (Plants), Mycetae (Fungi), and Animalia (Animals). Since then, there have been dramatic changes to the classifications of fungi, largely due to the appliance of phylogenetic molecular techniques. This has resulted in variances to the number of phylums, and the species assigned to them. Table 3.1 shows the seven phyla of the Fungi Kingdom. The majority of fungi pathogenic to humans inhabit the Ascomycota and Basidiomycota phyla. Fungi used to be dually named if they had a pleomorphic life cycle with sexual/ asexual stages (teleomorph/ anamorph, respectively), which meant that fungi often had two names and were classed differently. This practice was discontinued in January 2013 after the International Commission on the Taxonomy of Fungi decided that a ‘one fungus, one name’ approach should be followed. Fungi can be unicellular (yeast) or multicellular (fungi). Yeasts may look globose in nature when grown, whereas multicellular fungi grow as tubular, filamentous material called hyphae that can create a branching, hyphal network called a mycelium. Hyphae may have septa that cross their walls or be nonseptate, which is a method of differentiating fungi. An early hyphal outgrowth from a spore is called a germ tube. The germ tube test can be used to differentiate the yeasts Candida albicans and Candida dubliniensis from other Candida species. The fungal cell wall is composed of chitin and glucans, which are different components to the human cell wall. This means that they can be an effective target for antifungal therapy.

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