The Experts below are selected from a list of 60726 Experts worldwide ranked by ideXlab platform
Jean-paul Latgé - One of the best experts on this subject based on the ideXlab platform.
-
Revisiting Old Questions and New Approaches to Investigate the Fungal Cell Wall Construction.
Current topics in microbiology and immunology, 2020Co-Authors: Michael Blatzer, Anne Beauvais, Bernard Henrissat, Jean-paul LatgéAbstract:The beginning of our understanding of the Cell wall construction came from the work of talented biochemists in the 70–80’s. Then came the era of sequencing. Paradoxically, the accumulation of Fungal genomes complicated rather than solved the mystery of Cell wall construction, by revealing the involvement of a much higher number of proteins than originally thought. The situation has become even more complicated since it is now recognized that the Cell wall is an organelle whose composition continuously evolves with the changes in the environment or with the age of the Fungal Cell. The use of new and sophisticated technologies to observe Cell wall construction at an almost atomic scale should improve our knowledge of the Cell wall construction. This essay will present some of the major and still unresolved questions to understand the Fungal Cell wall biosynthesis and some of these exciting futurist approaches.
-
Potential of Chemically Synthesized Oligosaccharides To Define the Carbohydrate Moieties of the Fungal Cell Wall Responsible for the Human Immune Response, Using Aspergillus fumigatus Galactomannan as a Model.
mSphere, 2020Co-Authors: Sarah Sze Wah Wong, Jean-paul Latgé, Thierry Fontaine, Vadim B. Krylov, Dmitry A. Argunov, Alexander A. Karelin, Jean-phillipe Bouchara, Nikolay E. NifantievAbstract:Methodologies to identify epitopes or ligands of the Fungal Cell wall polysaccharides influencing the immune response of human pathogens have to date been imperfect. Using the galactomannan (GM) of Aspergillus fumigatus as a model, we have shown that synthetic oligosaccharides of distinct structures representing key fragments of Cell wall polysaccharides are the most precise tools to study the serological and immunomodulatory properties of a Fungal polysaccharide.
-
The Fungal Kingdom - The Fungal Cell Wall : Structure, Biosynthesis, and Function
Microbiology spectrum, 2017Co-Authors: Neil A. R. Gow, Jean-paul Latgé, Carol A. MunroAbstract:The molecular composition of the Cell wall is critical for the biology and ecology of each Fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major Cell wall components of Fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of Fungal walls. For similar reasons the enzymes that assemble Fungal Cell wall components are exCellent targets for antiFungal chemotherapies and fungicides. However, for Fungal pathogens, the Cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on Fungal Cell walls are moving from a descriptive phase defining the underlying genes and component parts of Fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of Cell walls and how the Cell wall is targeted by immune recognition systems and the design of antiFungal diagnostics and therapeutics.
-
the Fungal Cell wall structure biosynthesis and function
Microbiology spectrum, 2017Co-Authors: Jean-paul Latgé, Carol A. MunroAbstract:The molecular composition of the Cell wall is critical for the biology and ecology of each Fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major Cell wall components of Fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of Fungal walls. For similar reasons the enzymes that assemble Fungal Cell wall components are exCellent targets for antiFungal chemotherapies and fungicides. However, for Fungal pathogens, the Cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on Fungal Cell walls are moving from a descriptive phase defining the underlying genes and component parts of Fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of Cell walls and how the Cell wall is targeted by immune recognition systems and the design of antiFungal diagnostics and therapeutics.
-
Undressing the Fungal Cell Wall/Cell Membrane - the AntiFungal Drug Targets
Current pharmaceutical design, 2013Co-Authors: Rui Tada, Jean-paul Latgé, Vishukumar AimaniandaAbstract:Being external, the Fungal Cell wall plays a crucial role in the Fungal life. By covering the underneath Cell, it offers mechanical strength and acts as a barrier, thus protecting the fungus from the hostile environment. Chemically, this Cell wall is composed of different polysaccharides. Because of their specific composition, the Fungal Cell wall and its underlying plasma membrane are unique targets for the development of drugs against pathogenic Fungal species. The objective of this review is to consolidate the current knowledge on the antiFungal drugs targeting the Cell wall and plasma membrane, mainly of Aspergillus and Candida species – the most prevalent Fungal pathogens, and also to present challenges and questions conditioning the development of new antiFungal drugs targeting the Cell wall.
Carol A. Munro - One of the best experts on this subject based on the ideXlab platform.
-
The Fungal Kingdom - The Fungal Cell Wall : Structure, Biosynthesis, and Function
Microbiology spectrum, 2017Co-Authors: Neil A. R. Gow, Jean-paul Latgé, Carol A. MunroAbstract:The molecular composition of the Cell wall is critical for the biology and ecology of each Fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major Cell wall components of Fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of Fungal walls. For similar reasons the enzymes that assemble Fungal Cell wall components are exCellent targets for antiFungal chemotherapies and fungicides. However, for Fungal pathogens, the Cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on Fungal Cell walls are moving from a descriptive phase defining the underlying genes and component parts of Fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of Cell walls and how the Cell wall is targeted by immune recognition systems and the design of antiFungal diagnostics and therapeutics.
-
the Fungal Cell wall structure biosynthesis and function
Microbiology spectrum, 2017Co-Authors: Jean-paul Latgé, Carol A. MunroAbstract:The molecular composition of the Cell wall is critical for the biology and ecology of each Fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major Cell wall components of Fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of Fungal walls. For similar reasons the enzymes that assemble Fungal Cell wall components are exCellent targets for antiFungal chemotherapies and fungicides. However, for Fungal pathogens, the Cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on Fungal Cell walls are moving from a descriptive phase defining the underlying genes and component parts of Fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of Cell walls and how the Cell wall is targeted by immune recognition systems and the design of antiFungal diagnostics and therapeutics.
-
Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance
Mbio, 2015Co-Authors: Louise A Walker, Carol A. Munro, Marion Schiavone, Hélène Martin-yken, Etienne Dague, Alistair J. P. BrownAbstract:The Fungal Cell wall confers Cell morphology and protection against environmental insults. For Fungal pathogens, the Cell wall is a key immunological modulator and an ideal therapeutic target. Yeast Cell walls possess an inner matrix of interlinked -glucan and chitin that is thought to provide tensile strength and rigidity. Yeast Cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and Cell integrity (Mkc1, Cek1) signal- ing pathways. These mitogen-activated protein kinase (MAPK) pathways modulate Cell wall gene expression, leading to the con- struction of a new, modified Cell wall. We show that the Cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown Candida albicans Cells are more resistant to hyperosmotic shock than glucose-grown Cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most Cell death occurs within 10 min of osmotic shock. Sudden decreases in Cell volume drive rapid increases in Cell wall thickness. The elevated stress resistance of lactate-grown Cells correlates with reduced Cell wall elasticity, reflected in slower changes in Cell vol- ume following hyperosmotic shock. The Cell wall elasticity of lactate-grown Cells is increased by a triple mutation that inactivates the Crh family of Cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown Cells reduces Cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the Cell wall and with the ability of Cells to withstand osmotic shock. IMPORTANCE The C. albicans Cell wall is the first line of defense against external insults, the site of immune recognition by the host, and an attractive target for antiFungal therapy. Its tensile strength is conferred by a network of Cell wall polysaccharides, which are remodeled in response to growth conditions and environmental stress. However, little is known about how Cell wall elasticity is regulated and how it affects adaptation to stresses such as sudden changes in osmolarity. We show that elasticity is critical for survival under conditions of osmotic shock, before stress signaling pathways have time to induce gene expression and drive glycerol accumulation. Critical Cell wall remodeling enzymes control Cell wallflexibility, and its regulation is strongly de- pendent on host nutritional inputs. We also demonstrate an entirely new level of Cell wall dynamism, where significant architec- tural changes and structural realignment occur within seconds of an osmotic shock.
Juan Carlos Ribas - One of the best experts on this subject based on the ideXlab platform.
-
The Fungal Cell wall as a target for the development of new antiFungal therapies
Biotechnology advances, 2019Co-Authors: Juan Carlos G. Cortés, Pilar Pérez, M.-Ángeles Curto, Vanessa S. D. Carvalho, Juan Carlos RibasAbstract:In the past three decades invasive mycoses have globally emerged as a persistent source of healthcare-associated infections. The Cell wall surrounding the Fungal Cell opposes the turgor pressure that otherwise could produce Cell lysis. Thus, the Cell wall is essential for maintaining Fungal Cell shape and integrity. Given that this structure is absent in host mammalian Cells, it stands as an important target when developing selective compounds for the treatment of Fungal infections. Consequently, treatment with echinocandins, a family of antiFungal agents that specifically inhibits the biosynthesis of Cell wall (1-3)β-D-glucan, has been established as an alternative and effective antiFungal therapy. However, the existence of many pathogenic fungi resistant to single or multiple antiFungal families, together with the limited arsenal of available antiFungal compounds, critically affects the effectiveness of treatments against these life-threatening infections. Thus, new antiFungal therapies are required. Here we review the Fungal Cell wall and its relevance in biotechnology as a target for the development of new antiFungal compounds, disclosing the most promising Cell wall inhibitors that are currently in experimental or clinical development for the treatment of some invasive mycoses.
-
Fungal Cell Wall Analysis
Laboratory Protocols in Fungal Biology, 2012Co-Authors: Pilar Pérez, Juan Carlos RibasAbstract:Fungal Cell wall is a rigid structure mainly composed of polysaccharides (up to 90 %) and glycoproteins. It is essential for survival of the Fungal Cells, because it protects them against bursting caused by internal turgor pressure and against mechanical injury. Because of its absence in mammalian Cells, it is an attractive target for antiFungal agents. Thus, for various reasons, it might be important to know how the Cell wall is synthesized, and how to analyze its composition. We provide here information about in vitro analysis of the biosynthetic activities of the main Fungal wall and describe some methods for rapid analysis of Cell wall composition by using specific enzymatic degradations. We also describe some additional methods that can be occasionally used to analyze Fungal wall properties or composition. These methods provide powerful tools to evaluate changes in Fungal Cell walls and will be useful for screening new compounds for antiFungal activity that might cause inhibition of Cell wall biosynthesis and/or alter the structure of the Fungal Cell wall.
-
in vitro antiFungal activity of new series of homoallylamines and related compounds with inhibitory properties of the synthesis of Fungal Cell wall polymers
Bioorganic & Medicinal Chemistry, 2003Co-Authors: Leonor Vargas Y M, Juan Carlos Ribas, Maria Victoria Castelli, Vladimir V Kouznetsov, Juan Manuel Urbina G, Silvia N Lopez, Maximiliano Sortino, Ricardo D Enriz, Susana ZacchinoAbstract:The synthesis, in vitro antiFungal evaluation and SAR studies of 101 compounds of the 4-aryl-, 4-alkyl-, 4-pyridyl or -quinolinyl-4-N-arylamino-1-butenes series and related compounds, are reported here. Active structures showed to inhibit (1,3)-β-d-glucan and mainly chitin synthases, enzymes that catalyze the synthesis of the major Fungal Cell wall polymers.
-
in vitro antiFungal evaluation and structure activity relationships of a new series of chalcone derivatives and synthetic analogues with inhibitory properties against polymers of the Fungal Cell wall
Bioorganic & Medicinal Chemistry, 2001Co-Authors: Silvia N Lopez, Juan Carlos Ribas, Juan Carlos G. Cortés, Maria Victoria Castelli, Susana Zacchino, Jose N Dominguez, Gricela Lobo, Jaime Charrischarris, Cristina Devia, Ana RodriguezAbstract:Here we report the synthesis, in vitro antiFungal evaluation and SAR study of 41 chalcones and analogues. In addition, all active structures were tested for their capacity of inhibiting Saccharomyces cerevisiae β(1,3)-glucan synthase and chitin synthase, enzymes that catalyze the synthesis of the major polymers of the Fungal Cell wall.
Stephen J. Free - One of the best experts on this subject based on the ideXlab platform.
-
Fungal Cell wall organization and biosynthesis
Advances in Genetics, 2013Co-Authors: Stephen J. FreeAbstract:The composition and organization of the Cell walls from Saccharomyces cerevisiae, Candida albicans, Aspergillus fumigatus, Schizosaccharomyces pombe, Neurospora crassa, and Cryptococcus neoformans are compared and contrasted. These Cell walls contain chitin, chitosan, β-1,3-glucan, β-1,6-glucan, mixed β-1,3-/β-1,4-glucan, α-1,3-glucan, melanin, and glycoproteins as major constituents. A comparison of these Cell walls shows that there is a great deal of variability in Fungal Cell wall composition and organization. However, in all cases, the Cell wall components are cross-linked together to generate a Cell wall matrix. The biosynthesis and properties of each of the major Cell wall components are discussed. The chitin and glucans are synthesized and extruded into the Cell wall space by plasma membrane-associated chitin synthases and glucan synthases. The glycoproteins are synthesized by ER-associated ribosomes and pass through the canonical secretory pathway. Over half of the major Cell wall proteins are modified by the addition of a glycosylphosphatidylinositol anchor. The Cell wall glycoproteins are also modified by the addition of O-linked oligosaccharides, and their N-linked oligosaccharides are extensively modified during their passage through the secretory pathway. These Cell wall glycoprotein posttranslational modifications are essential for cross-linking the proteins into the Cell wall matrix. Cross-linking the Cell wall components together is essential for Cell wall integrity. The activities of four groups of cross-linking enzymes are discussed. Cell wall proteins function as cross-linking enzymes, structural elements, adhesins, and environmental stress sensors and protect the Cell from environmental changes.
-
The structure and synthesis of the Fungal Cell wall
BioEssays, 2006Co-Authors: Shaun M. Bowman, Stephen J. FreeAbstract:The Fungal Cell wall is a dynamic structure that protects the Cell from changes in osmotic pressure and other environmental stresses, while allowing the Fungal Cell to interact with its environment. The structure and biosynthesis of a Fungal Cell wall is unique to the fungi, and is therefore an exCellent target for the development of anti-Fungal drugs. The structure of the Fungal Cell wall and the drugs that target its biosynthesis are reviewed. Based on studies in a number of fungi, the Cell wall has been shown to be primarily composed of chitin, glucans, mannans and glycoproteins. The biosynthesis of the various components of the Fungal Cell wall and the importance of the components in the formation of a functional Cell wall, as revealed through mutational analyses, are discussed. There is strong evidence that the chitin, glucans and glycoproteins are covalently cross-linked together and that the cross-linking is a dynamic process that occurs extraCellularly. BioEssays 28: 799–808, 2006. © 2006 Wiley Periodicals, Inc.
Stuart M. Levitz - One of the best experts on this subject based on the ideXlab platform.
-
Exploiting Fungal Cell wall components in vaccines
Seminars in Immunopathology, 2015Co-Authors: Stuart M. Levitz, Haibin Huang, Gary R. Ostroff, Charles A. SpechtAbstract:Innate recognition of fungi leads to strong adaptive immunity. Investigators are trying to exploit this observation in vaccine development by combining antigens with evolutionarily conserved Fungal Cell wall carbohydrates to induce protective responses. Best studied is β-1,3-glucan, a glycan that activates complement and is recognized by dectin-1. Administration of antigens in association with β-1,3-glucan, either by direct conjugation or complexed in glucan particles, results in robust humoral and Cellular immune responses. While the host has a host of mannose receptors, responses to Fungal mannoproteins generally are amplified if Cells are cooperatively stimulated with an additional danger signal such as a toll-like receptor agonist. Chitosan, a polycationic homopolymer of glucosamine manufactured by the deacetylation of chitin, is being studied as an adjuvant in DNA and protein-based vaccines. It appears particularly promising in mucosal vaccines. Finally, universal and organism-specific Fungal vaccines have been formulated by conjugating Fungal Cell wall glycans to carrier proteins. A major challenge will be to advance these experimental findings so that at risk patients can be protected.
-
Innate recognition of Fungal Cell walls.
PLoS pathogens, 2010Co-Authors: Stuart M. LevitzAbstract:The emergence of Fungal infections as major causes of morbidity and mortality in immunosuppressed individuals has prompted studies into how the host recognizes Fungal pathogens. Fungi are eukaryotes and as such share many similarities with mammalian Cells. The most striking difference, though, is the presence of a Cell wall that serves to protect the fungus from environmental stresses, particularly osmotic changes [1]. This task is made challenging because the fungus must remodel itself to allow for Cell growth and division, including the conversion to different morphotypes, such as occurs during germination of spherical spores into filamentous hyphae. The Cell wall also connects the fungus with its environment by triggering intraCellular signaling pathways and mediating adhesion to other Cells and extraCellular matrices. Here, important facts and concepts critical for understanding innate sensing of the Fungal Cell wall by mammalian pathogens are reviewed.
-
Recognition of the Fungal Cell wall by innate immune receptors
Current Fungal Infection Reports, 2009Co-Authors: Stuart M. Levitz, Charles A. SpechtAbstract:Human Cells have a variety of receptors that innately recognize conserved structures on the Fungal Cell wall. Major receptors include dectin-1, which recognizes β1,3-glucans; mannose receptors, which recognize mannans, and Toll-like receptors 2 and 4. The Fungal Cell wall is a potent activator of complement, which results in deposition of fragments of the third component of complement that serve as ligands for complement receptors. The nature of the innate immune response is dictated by the relative amount each of these receptors is stimulated. Innate recognition can lead to destruction of the invading fungus and/or initiation of an adaptive immune response. Fungi have a variety of strategies to avoid innate recognition, including masking of ligands and changing their surface properties by phase transition.
