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Synthetic Oligosaccharides Mimicking Fungal Cell Wall Polysaccharides.
Krylov, VB, Nifantiev, NE
Current topics in microbiology and immunology. 2020;:1-16
Abstract
The cell wall of pathogenic fungi is highly important for the development of fungal infections and is the first cellular component to interact with the host immune system. The fungal cell wall is mainly built up of different polysaccharides representing ligands for pattern recognition receptors (PRRs) on immune cells and antibodies. Purified fungal polysaccharides are not easily available; in addition, they are structurally heterogenic and have wide molecular weight distribution that limits the possibility to use natural polysaccharides to assess the structure of their active determinants. The synthetic oligosaccharides of definite structure representing distinct polysaccharide fragments are indispensable tools for a variety of biological investigations and represent an advantageous alternative to natural polysaccharides. The attachment of a spacer group to these oligosaccharides permits their efficient transformation into immunogenic glycoconjugates as well as their immobilization on plates or microbeads. Herein, we summarize current information on synthetic availability of the variety of oligosaccharides related to main types of fungal cell wall components: galactomannan, α- and β-mannan, α- and β-(1 → 3)-glucan, chitin, chitosan, and others. These data are supplemented with published results of biochemical and immunological applications of synthetic oligosaccharides as molecular probes especially as the components of thematic glycoarrays suitable for characterization of anti-polysaccharide antibodies and cellular lectins or PRRs.
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2.
Scedosporium Cell Wall: From Carbohydrate-Containing Structures to Host-Pathogen Interactions.
Rollin-Pinheiro, R, Xisto, MIDDS, Rochetti, VP, Barreto-Bergter, E
Mycopathologia. 2020;(6):931-946
Abstract
Scedosporium species are filamentous fungi usually found in sewage and soil from human-impacted areas. They cause a wide range of diseases in humans, from superficial infections, such as mycetoma, to invasive and disseminated cases, especially associated in immunocompromised patients. Scedosporium species are also related to lung colonization in individuals presenting cystic fibrosis and are considered one of the most frequent fungal pathogens associated to this pathology. Scedosporium cell wall contains glycosylated molecules involved in important biological events related to virulence and pathogenicity and represents a significant source of antigens. Polysaccharides, peptidopolysaccharides, O-linked oligosaccharides and glycosphingolipids have been identified on the Scedosporium surface. Their primary structures were determined based on a combination of techniques including gas chromatography, ESI-MS, and 1H and 13C nuclear magnetic resonance. Peptidorhamnnomannans are common cell wall components among Scedosporium species. Comparing different species, minor structural differences in the carbohydrate portions were detected which could be useful to understand variations in virulence observed among the species. N- and O-linked peptidorhamnomannans are major pathogen-associated molecular patterns and, along with α-glucans, play important roles in triggering host innate immunity. Glycosphingolipids, such as glucosylceramides, have highly conserved structures in Scedosporium species and are crucial for fungal growth and virulence. The present review presents current knowledge on structural and functional aspects of Scedosporium glycoconjugates that are relevant for understanding pathogenicity mechanisms and could contribute to the design of new agents capable of inhibiting growth and differentiation of Scedosporium species. Other cell components such as melanin and ectophosphatases will be also included.
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3.
A Report on Fungal (1→3)-α-d-glucans: Properties, Functions and Application.
Złotko, K, Wiater, A, Waśko, A, Pleszczyńska, M, Paduch, R, Jaroszuk-Ściseł, J, Bieganowski, A
Molecules (Basel, Switzerland). 2019;(21)
Abstract
The cell walls of fungi are composed of glycoproteins, chitin, and α- and β-glucans. Although there are many reports on β-glucans, α-glucan polysaccharides are not yet fully understood. This review characterizes the physicochemical properties and functions of (1→3)-α-d-glucans. Particular attention has been paid to practical application and the effect of glucans in various respects, taking into account unfavourable effects and potential use. The role of α-glucans in plant infection has been proven, and collected facts have confirmed the characteristics of Aspergillus fumigatus infection associated with the presence of glucan in fungal cell wall. Like β-glucans, there are now evidence that α-glucans can also stimulate the immune system. Moreover, α-d-glucans have the ability to induce mutanases and can thus decompose plaque.
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4.
Vitamin C: A Natural Inhibitor of Cell Wall Functions and Stress Response in Mycobacteria.
Syal, K, Chatterji, D
Advances in experimental medicine and biology. 2018;:321-332
Abstract
Tuberculosis, caused by Mycobacterium tuberculosis, has re-emerged as a threat to human race. Conventional antibiotic treatments are failing due to different stress response strategies adopted by bacterial pathogens. Since time immemorial, Vitamin C is known to protect against pathogens by boosting immunity in humans. Recently, Vitamin C has been shown to directly kill M. tuberculosis including multiple drug-resistant strains by generation of oxidative radicals through Fenton's reaction. Concurrently, it inhibits (p)ppGpp-mediated stringent response thus effectively shutting down long-term survival and persistence in mycobacteria. Here, we have discussed historical perspective and recent evidences on Vitamin C-mediated inhibition of several key pathways of M. tuberculosis such as (p)ppGpp synthesis and mycobacterial cell wall function. Several cell wall components including mycolic acids are critical for mycobacterial virulence. We observed downregulation of various mycolic acids in M. smegmatis upon treatment with Vitamin C, and data have been presented here. Vitamin C has been shown to inhibit the biofilm growth as well as disrupt the formed biofilm in mycobacteria. Additionally, Vitamin C role in cell-mediated and humoral immunity has been elucidated. Vitamin C is toxic at high concentration; therefore we have proposed the idea of derivatizing Vitamin C in order to lower the minimal inhibition concentration (MIC) necessary to target M. tuberculosis.
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5.
Spatial Organization of Cell Wall-Anchored Proteins at the Surface of Gram-Positive Bacteria.
Dramsi, S, Bierne, H
Current topics in microbiology and immunology. 2017;:177-201
Abstract
Bacterial surface proteins constitute an amazing repertoire of molecules with important functions such as adherence, invasion, signalling and interaction with the host immune system or environment. In Gram-positive bacteria, many surface proteins of the "LPxTG" family are anchored to the peptidoglycan (PG) by an enzyme named sortase. While this anchoring mechanism has been clearly deciphered, less is known about the spatial organization of cell wall-anchored proteins in the bacterial envelope. Here, we review the question of the precise spatial and temporal positioning of LPxTG proteins in subcellular domains in spherical and ellipsoid bacteria (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae and Enterococcus faecalis) and in the rod-shaped bacterium Listeria monocytogenes. Deposition at specific sites of the cell wall is a dynamic process tightly connected to cell division, secretion, cell morphogenesis and levels of gene expression. Studying spatial occupancy of these cell wall-anchored proteins not only provides information on PG dynamics in responses to environmental changes, but also suggests that pathogenic bacteria control the distribution of virulence factors at specific sites of the surface, including pole, septa or lateral sites, during the infectious process.
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6.
A review about brown algal cell walls and fucose-containing sulfated polysaccharides: Cell wall context, biomedical properties and key research challenges.
Deniaud-Bouët, E, Hardouin, K, Potin, P, Kloareg, B, Hervé, C
Carbohydrate polymers. 2017;:395-408
Abstract
Studies on brown algal cell walls have entered a new phase with the concomitant discovery of novel polysaccharides present in cell walls and the establishment of a comprehensive generic model for cell wall architecture. Brown algal cell walls are composites of structurally complex polysaccharides. In this review we discuss the most recent progress in the structural composition of brown algal cell walls, emphasizing the significance of extraction and screening techniques, and the biological activities of the corresponding polysaccharides, with a specific focus on the fucose-containing sulfated polysaccharides. They include valuable marine molecules that exert a broad range of pharmacological properties such as antioxidant and anti-inflammatory activities, functions in the regulation of immune responses and of haemostasis, anti-infectious and anticancer actions. We identify the key remaining challenges in this research field.