scholarly journals Assembly of Peptidoglycan Fragments—A Synthetic Challenge

2020 ◽  
Vol 13 (11) ◽  
pp. 392
Author(s):  
Fausto Queda ◽  
Gonçalo Covas ◽  
Sérgio Filipe ◽  
M. Marques

Peptidoglycan (PGN) is a major constituent of most bacterial cell walls that is recognized as a primary target of the innate immune system. The availability of pure PGN molecules has become key to different biological studies. This review aims to (1) provide an overview of PGN biosynthesis, focusing on the main biosynthetic intermediates; (2) focus on the challenges for chemical synthesis posed by the unique and complex structure of PGN; and (3) cover the synthetic routes of PGN fragments developed to date. The key difficulties in the synthesis of PGN molecules mainly involve stereoselective glycosylation involving NAG derivatives. The complex synthesis of the carbohydrate backbone commonly involves multistep sequences of chemical reactions to install the lactyl moiety at the O-3 position of NAG derivatives and to control enantioselective glycosylation. Recent advances are presented and synthetic routes are described according to the main strategy used: (i) based on the availability of starting materials such as glucosamine derivatives; (ii) based on a particular orthogonal synthesis; and (iii) based on the use of other natural biopolymers as raw materials.

1974 ◽  
Vol 140 (1) ◽  
pp. 47-55 ◽  
Author(s):  
David Jones ◽  
Alex. H. Gordon ◽  
John S. D. Bacon

1. Two fungi, Coniothyrium minitans Campbell and Trichoderma viride Pers. ex Fr., were grown on autoclaved crushed sclerotia of the species Sclerotinia sclerotiorum, which they parasitize. 2. in vitro the crude culture filtrates would lyse walls isolated from hyphal cells or the inner pseudoparenchymatous cells of the sclerotia, in which a branched β-(1→3)-β-(1→6)-glucan, sclerotan, is a major constituent. 3. Chromatographic fractionation of the enzymes in each culture filtrate revealed the presence of several laminarinases, the most active being an exo-β-(1→3)-glucanase, known from previous studies to attack sclerotan. Acting alone this brought about a limited degradation of the glucan, but the addition of fractions containing an endo-β-(1→3)-glucanase led to almost complete breakdown. A similar synergism between the two enzymes was found in their lytic action on cell walls. 4. When acting alone the endo-β-(1→3)-glucanase had a restricted action, the products including a trisaccharide, tentatively identified as 62-β-glucosyl-laminaribiose. 5. These results are discussed in relation to the structure of the cell walls and of their glucan constituents.


2021 ◽  
pp. 13-19
Author(s):  
Amita Singh ◽  
Raj Kumar ◽  
S. K. Kannaujia ◽  
Manikrishna Manikrishna ◽  
N. P. Singh

Abhrak bhasma (AB) is a type of bhasma prepared from repeated incineration of mineral mica with decoctions of about 72 herbs. The particle size of Abhrak bhasm has been shown to be in the range of 29-88 nanometers and Fe, Ca, Si, Mg and K are found to be as major constituent. Many drugs developed to treat Central Nervous System (CNS) disorders are unable to reach the brain parenchyma in therapeutically relevant concentrations. The blood brain barrier protects brain parenchyma from the uctuation of plasma composition, from pathogenic agents and maintains homeostasis of the brain parenchyma by restricting non-specic ux of ions, peptides, proteins and even cells into and out the brain. Immunohistochemistry is being widely employed as a tool for biological studies. This study is conducted to examine the change in the continuity of Blood brain barrier by using immunohistochemistry, once Abhrak bhasm drug is given in experimental animal and also to examine the histology of organs. In this study a total of 30 adult albino Wistar rats of approximately 4 months age (approx. 150-200 gms) of either sex selected randomly to see the effect of Abhrak bhasm, an ayurvedic drug on Wistar rats. The rats were weighed, marked and divided into 5 groups each consisting of six animals. In normal control group (Group E), no drug was administered and in rest of the four treated groups (Group-A,B,C,D), Abhrak bhasm @ 36 mg/kg B.wt. was administered orally once in each rat. Brain, liver, kidneys,spleen and blood samples were collected in 10% formalin solution after euthanizing the rats at 0.5,2,6 & 12 hours of Abhrak bhasma drug intervention. The alterations in any of the biochemical parameters are within the tolerable limits of liver and kidney since the dose of abhrak bhasm did not affect liver and kidneys. In the present study, the increase in ALP level may be the result of alterations in metabolisms that occurred without any signicant alteration in histology of liver. After applying the immunohistochemistry with the research markers GFAP, CD 34, S 100, GLUT-1 and RECA-1 on the rats in groups A,B,C and D, there was no change in the intensity of immunohistochemistry, with respect to control. While on applying the Occludin, the intensity of immunohistochemistry was reduced in all the treatment groups as compared to the control group. On the basis of ndings of present study it can be concluded that the therapeutic dose of Abhrak bhasma causes changes at the level of tight junctions present in blood brain barrier in rats which is shown by immunohistochemistry with occludin research marker. There is no toxic effect of drug on different organs of rats as no signicant changes in histology of organs are seen. More studies need to be done to check the permeability of blood brain barrier for Abhrak bhasma drug, like calculating its concentration in brain tissues and other vital organs of rat.


Author(s):  
Tetiana Oproshanska ◽  
Olga Khvorost ◽  
Kateryna Skrebtsova ◽  
Konradas Vitkevicius

The aim is to conduct a comparative pharmacognostical study of the series of roots of Rosa (R.) majalis Herrm. and Rosa (R.) canina L. with the establishment of diagnostic features of morphological and anatomical structure and boundary limits of numerical indicators of raw materials. Materials and methods. The fresh and dry raw materials were used to study the macroscopic microscopic features by microscope Delta optical BioLight 300 (Poland). Determination of total polyphenols was performed by spectrophotometry (on a spectrophotometer Optizen POP (Korea)) and HPLC (chromatograph an Agilent 1200 3 D LC System Technologies (USA)). Results. The morphological (nature of the surface (periderm) and fracture) and anatomical (color of cell walls and their cavities; location of the sclerenchyma; the presence of a crystalline coating of the sclerenchyma at the root of R. canina; of various elements of the remains of the tetraarchic conducting bundle in the center of the root) diagnostical features of roots of R. majalis and R. Canina were established. Comparing the numerical values of loss on drying (not more than 10 %), total ash (not more than 5 %), extractable matter (not less than 9 %) and the quantitative content of total polyphenols (not less than 4 %) it was determined that both types of raw materials according to these indicators are almost indistinguishable. Conclusions. Loss on drying, total ash, extractable matter and content of total polyphenols of the root of R. majalis and R. canina do not have significant differences, that is why the root of both plant species can be used as medicinal plant raw materials such as “Rose root”. The obtained data will be used in further research when creating methods of quality control of plant raw materials and phytomedicines


STORIA URBANA ◽  
2009 ◽  
pp. 83-100
Author(s):  
Manuel Vaquero Pineiro

- The different forms of presence of Spanish merchants in Rome since the beginning of Early Modern Age: ideas for a debate at European level. Between the 15th and the 16th centuries, due also to the political coverage offered by the empire of Charles V, both Castilians and Catalans succeeded in establishing themselves as the most dynamic merchants in Europe. The control they had over strategic raw materials such as wool, iron and alum and their privileged position gave them easy access to monetary flows in the coastal cities from Flanders to the Mediterranean, where a number Spanish colonies were established. These cities were soon granted with major privileges by local authorities, which fostered the settling of merchants and bankers in certain areas therein. The result, as in the case of Bruges, was the creation of districts protected by exclusive jurisdictional rights or, as in the case of Rome, a random scattering of the new settlers, with no real reference points. In the mid 16th century, in Rome the distribution of places of work and residence followed no national or religious criteria. The complex structure of social relations was thus reflected also in Rome topography.


2018 ◽  
Vol 56 ◽  
pp. 04003
Author(s):  
Sergei Tkach

The article deals with the problems of mineral raw material losses of quality and quantity management in developing of large-scale complex-structure and composition deposits of solid minerals. It is shown that a very high degree of mining and geological conditions variability in time and space for the development of mining units is typical for such deposits. This significantly complicates the qualitative and quantitative operating losses setting and accounting of mineral raw materials during its extraction in the framework of existing general and industry regulatory documents. Conceptual principles for face-by-face operational setting of losses and impoverishment of minerals for the conditions of bulk mining of complex-structure deposits with the formation of gross mining flow with economically feasible and specified level of quality (the content of commercial and harmful components) are stated. These principles generally do not contradict effective instructions main provisions and are made to minimize the total operating losses during the processing of several mine sections (faces).


2016 ◽  
Vol 27 (6) ◽  
pp. 1002-1014 ◽  
Author(s):  
Jia Lin ◽  
Michael J. Wester ◽  
Matthew S. Graus ◽  
Keith A. Lidke ◽  
Aaron K. Neumann

The cell wall of Candida albicans is composed largely of polysaccharides. Here we focus on β-glucan, an immunogenic cell-wall polysaccharide whose surface exposure is often restricted, or “masked,” from immune recognition by Dectin-1 on dendritic cells (DCs) and other innate immune cells. Previous research suggested that the physical presentation geometry of β-glucan might determine whether it can be recognized by Dectin-1. We used direct stochastic optical reconstruction microscopy to explore the fine structure of β-glucan exposed on C. albicans cell walls before and after treatment with the antimycotic drug caspofungin, which alters glucan exposure. Most surface-accessible glucan on C. albicans yeast and hyphae is limited to isolated Dectin-1–binding sites. Caspofungin-induced unmasking caused approximately fourfold to sevenfold increase in total glucan exposure, accompanied by increased phagocytosis efficiency of DCs for unmasked yeasts. Nanoscopic imaging of caspofungin-unmasked C. albicans cell walls revealed that the increase in glucan exposure is due to increased density of glucan exposures and increased multiglucan exposure sizes. These findings reveal that glucan exhibits significant nanostructure, which is a previously unknown physical component of the host– Candida interaction that might change during antifungal chemotherapy and affect innate immune activation.


2020 ◽  
Author(s):  
Klare L. Bersch ◽  
Kristen E. DeMeester ◽  
Rachid Zagani ◽  
Kimberly A. Wodzanowski ◽  
Hans-Christian Reinecker ◽  
...  

ABSTRACTThe human innate immune system responds to both pathogen and commensal bacteria at the molecular level using bacterial peptidoglycan (PG) recognition elements. Traditionally, synthetic and commercially accessible PG monosaccharide units known as muramyl dipeptide (MDP) and N-glycolyl MDP (ng-MDP) have been used to probe the mechanism of innate immune activation of pattern recognition receptors (PRRs) such as NOD-like receptors (NLRs). However, bacterial PG is a dynamic and complex structure, with various chemical modifications and trimming mechanisms that result in the production of disaccharide containing elements. These molecules pose as attractive targets for immunostimulatory screening; however, studies are limited due to their synthetic accessibility. Inspired by disaccharide containing compounds produced from the gut microbe, Lactobacillus acidophilus, a robust and scalable chemical synthesis of PG-based disaccharide ligands was implemented. Together with a monosaccharide PG library, compounds were screened for their ability to stimulate proinflammatory genes in bone marrow derived macrophages (BMDMs). The data reveal a diverse gene induction pattern between monosaccharide and disaccharide PG units, suggesting that PG innate immune signaling is more complex than a one-activator-one pathway program, as biologically relevant fragments induce distinct transcriptional programs. These disaccharide molecules will serve as critical immunostimulatory tools to more precisely define specialized innate immune regulatory mechanisms that distinguish between commensal and pathogenic bacteria residing in the microbiome.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Tian ◽  
Chien-Yuan Lin ◽  
Joon-Hyun Park ◽  
Chuan-Yin Wu ◽  
Ramu Kakumanu ◽  
...  

Abstract Background The development of bioenergy crops with reduced recalcitrance to enzymatic degradation represents an important challenge to enable the sustainable production of advanced biofuels and bioproducts. Biomass recalcitrance is partly attributed to the complex structure of plant cell walls inside which cellulose microfibrils are protected by a network of hemicellulosic xylan chains that crosslink with each other or with lignin via ferulate (FA) bridges. Overexpression of the rice acyltransferase OsAT10 is an effective bioengineering strategy to lower the amount of FA involved in the formation of cell wall crosslinks and thereby reduce cell wall recalcitrance. The annual crop sorghum represents an attractive feedstock for bioenergy purposes considering its high biomass yields and low input requirements. Although we previously validated the OsAT10 engineering approach in the perennial bioenergy crop switchgrass, the effect of OsAT10 expression on biomass composition and digestibility in sorghum remains to be explored. Results We obtained eight independent sorghum (Sorghum bicolor (L.) Moench) transgenic lines with a single copy of a construct designed for OsAT10 expression. Consistent with the proposed role of OsAT10 in acylating arabinosyl residues on xylan with p-coumarate (pCA), a higher amount of p-coumaroyl-arabinose was released from the cell walls of these lines upon hydrolysis with trifluoroacetic acid. However, no major changes were observed regarding the total amount of pCA or FA esters released from cell walls upon mild alkaline hydrolysis. Certain diferulate (diFA) isomers identified in alkaline hydrolysates were increased in some transgenic lines. The amount of the main cell wall monosaccharides glucose, xylose, and arabinose was unaffected. The transgenic lines showed reduced lignin content and their biomass released higher yields of sugars after ionic liquid pretreatment followed by enzymatic saccharification. Conclusions Expression of OsAT10 in sorghum leads to an increase of xylan-bound pCA without reducing the overall content of cell wall FA esters. Nevertheless, the amount of total cell wall pCA remains unchanged indicating that most pCA is ester-linked to lignin. Unlike other engineered plants overexpressing OsAT10 or a phylogenetically related acyltransferase with similar putative function, the improvements of biomass saccharification efficiency in sorghum OsAT10 lines are likely the result of lignin reductions rather than reductions of cell wall-bound FA. These results also suggest a relationship between xylan-bound pCA and lignification in cell walls.


2020 ◽  
Vol 21 (11) ◽  
pp. 4178
Author(s):  
Paweł Kwiatkowski ◽  
Bartosz Wojciuk ◽  
Iwona Wojciechowska-Koszko ◽  
Łukasz Łopusiewicz ◽  
Bartłomiej Grygorcewicz ◽  
...  

The study aimed to analyze morphological and functional changes of Staphylococcus aureus cells due to trans-anethole (a terpenoid and the major constituent of fennel, anise, or star anise essential oils) exposition, and their consequences for human neutrophils phagocytic activity as well as IL-8 production (recognized as the major chemoattractant). The investigation included the evaluation of changes occurring in S. aureus cultures, i.e., staphyloxanthin production, antioxidant activities, cell size distribution, and cells composition as a result of incubation with trans-anethole. It was found that the presence of trans-anethole in the culture medium reduced the level of staphyloxanthin production, as well as decreased antioxidant activities. Furthermore, trans-anethole-treated cells were characterized by larger size and a tendency to diffuse in comparison to the non-treated cells. Several cell components, such as phospholipids and peptidoglycan, were found remarkably elevated in the cultures treated with trans-anethole. As a result of the aforementioned cellular changes, the bacteria were phagocytized by neutrophils more efficiently (ingestion and parameters associated with killing activity were at a higher level as compared to the control system). Additionally, IL-8 production was at a higher level for trans-anethole modified bacteria. Our results suggest that trans-anethole represents a promising measure in combating severe staphylococcal infections, which has an important translational potential for clinical applications.


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