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Microbial Pathogenesis Nov 2022The ptsG (hpIIBC) gene, belonging to the glucose-specific phosphotransferase system, encodes the bacterial glucose-specific enzyme IIBC. In this study, the effects of a...
The ptsG (hpIIBC) gene, belonging to the glucose-specific phosphotransferase system, encodes the bacterial glucose-specific enzyme IIBC. In this study, the effects of a deletion of the ptsG gene were investigated by metabolome and transcriptome analyses. At the transcriptional level, we identified 970 differentially expressed genes between ΔptsG and sc1401 (Padj<0.05) and 2072 co-expressed genes. Among these genes, those involved in methane metabolism, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, pyruvate metabolism, phosphotransferase system (PTS), biotin metabolism, Two-component system and Terpenoid backbone biosynthesis showed significant changes in the ΔptsG mutant strain. Metabolome analysis revealed that a total of 310 metabolites were identified, including 20 different metabolites (p < 0.05). Among them, 15 metabolites were upregulated and 5 were downregulated in ΔptsG mutant strain. Statistical analysis revealed there were 115 individual metabolites having correlation, of which 89 were positive and 26 negative. These metabolites include amino acids, phosphates, amines, esters, nucleotides, benzoic acid and adenosine, among which amino acids and phosphate metabolites dominate. However, not all of these changes were attributable to changes in mRNA levels and must also be caused by post-transcriptional regulatory processes. The knowledge gained from this lays the foundation for further study on the role of ptsG in the pathogenic process of Glaesserella parasuis (G.parasuis).
Topics: Adenosine; Amines; Amino Acids; Amino Sugars; Benzoates; Biotin; Glucose; Metabolome; Methane; Nucleotides; Phosphates; Phosphoenolpyruvate Sugar Phosphotransferase System; Pyruvates; RNA, Messenger; Starch; Sucrose; Terpenes; Transcriptome; Pasteurellaceae
PubMed: 36150554
DOI: 10.1016/j.micpath.2022.105785 -
Journal of Functional Biomaterials Nov 2022Amino sugars N-acetylglucosamine (GlcNAc) and glucosamine (GlcN) are abundant sources of carbon and nitrogen in the oral cavity. The aim of this study was to investigate...
Amino sugars N-acetylglucosamine (GlcNAc) and glucosamine (GlcN) are abundant sources of carbon and nitrogen in the oral cavity. The aim of this study was to investigate the effects of GlcNAc metabolism on the genomics and biochemistry of a saliva-derived microbial community, and on the surface integrity of human teeth and restorative surfaces. Pooled cell-containing saliva (CCS) was used to establish a microcosm biofilm in vitro in a biofilm medium (BM) containing 5 different carbohydrates. The microbial composition of each biofilm was analyzed by 16S rRNA amplicon sequencing, and the concentrations of eight organic acids were determined for selected sugars by targeted metabolomics. Meanwhile, extracted human teeth and polished titanium and ceramic disks were submerged in BM supplemented with 1% of glucose or GlcNAc, inoculated with CCS and Streptococcus mutans UA159, and incubated for 30 days. To mimic the effects of other microbial byproducts, the specimens were immersed in 10 mM hydrogen peroxide and 10 mM ammonium hydroxide for 30 days. The surface of each specimen was evaluated by profilometry for roughness (Ra) and imaged by scanning electron microscopy. The pH of the biofilm supernatant was significantly higher for the medium containing GlcNAc (p < 0.0001), and was higher in samples containing teeth than the two restorative disks for media containing the same sugar. For both teeth and titanium specimens, the samples treated with glucose-biofilm presented higher roughness values (Ra) than those with GlcNAc-biofilm and every other group. SEM images of the teeth and titanium disks largely supported the profilometry results, with glucose-biofilm samples demonstrating the largest deviation from the reference. For ceramic disks, slightly higher Ra values were obtained for the ammonia group. These findings provide the first direct evidence to support the ability of amino sugars to significantly reduce the cariogenic potential of oral biofilms by altering their biochemistry and bacterial composition. Additionally, amino sugar metabolism appears to be less detrimental to teeth and restorative surfaces than glucose metabolism.
PubMed: 36412864
DOI: 10.3390/jfb13040223 -
Scientific Reports Sep 2022Soil organic matter (SOM) is of vital importance to soil health, and also plays a crucial role in the quality of the crops such as tobacco. However, the link between...
Soil organic matter (SOM) is of vital importance to soil health, and also plays a crucial role in the quality of the crops such as tobacco. However, the link between tobacco quality and SOM chemical compositions is still not well understood. To fill the information gap, we analyzed the quality of tobacco leaves and the corresponding SOM molecular compositions by electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), that were collected from six different sites in Bijie, Guizhou Province, China. The tobacco quality variedin six sites based on their chemical compositions. SOM compounds had a remarked impact on the quality of tobacco leaves and a distinct difference in SOM composition between low-quality and high-quality tobacco leaves was observed as well. Specifically, 105 common molecular formulas were detected in three SOM compounds of high-quality tobacco, which were more than those in low-quality samples. Although amino sugar, proteins, lipids, tannins, and carbohydrates had a collective influence on the chemical composition of tobacco leaves, the effect contributed by amino sugar and tannins was more prominent. In summary, fully understanding the association between tobacco chemical composition and SOM compounds can provide new insight into the regulation of tobacco quality and the sustainable development of agriculture.
Topics: Agriculture; Amino Sugars; Organic Chemicals; Soil; Tannins; Nicotiana
PubMed: 36097148
DOI: 10.1038/s41598-022-19428-6 -
Journal of Food Biochemistry Aug 2022The crude Hedysarum polysaccharides (HPS: HPS-50 and HPS-80) obtained from Radix Hedysari exhibited great pharmacological activities in our previous research. This study...
The crude Hedysarum polysaccharides (HPS: HPS-50 and HPS-80) obtained from Radix Hedysari exhibited great pharmacological activities in our previous research. This study investigated the effects of HPS on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury (ALI) in mice and LPS-induced injury in LO2 cells, as well as the relationship between structural characteristics and hepatoprotective activities. The in vivo results showed that compared with HPS-80, HPS-50 showed stronger hepatoprotection, which improved histopathological changes to normal levels. HPS-50 significantly decreased the levels of ALT, AST, MPO, and MDA, increased the activities of SOD, CAT, and GSH, and suppressed the LPS/D-GalN-triggered production of TNF-α, IL-1β, and IL-6 (p < .05). The results in vitro showed that HPS-50-P (HPS-50-1, HPS-50-2, and HPS-50-3) purified from HPS-50 played significant protective roles against LPS-induced injury in LO2 cells by reducing cell apoptosis and relieving cell cycle arrest. HPS-50-2 restored the percentage of normal cells from 54.8% to 94.7%, and reduced the S phase cells from 59.40% to 47.05% (p < .01). By analyzing the structure of HPS-50-P, including monosaccharide composition, molecular weight, chain conformation, and surface morphology, we speculated that the best protective effect of HPS-50-2 might be attributed to its beta configuration, highest molecular weight, and high glucose and galactose contents. These findings indicate that HPS-50 might be a promising source of functional foods for the protection and prevention of ALI. PRACTICAL APPLICATIONS: In this study, the protective effect of HPS on ALI was evaluated from multiple perspectives, and HPS-50-2 was screened as a potential active ingredient. This study has two practical applications. First, it provides a new way to improve ALI, and a new option for patients to prevent and treat ALI. Second, this work also complements the pharmacological activity of Radix Hedysari and provides a basis for the development of Radix Hedysari as a functional food.
Topics: Animals; Fabaceae; Galactosamine; Lipopolysaccharides; Liver; Mice; Polysaccharides
PubMed: 35484857
DOI: 10.1111/jfbc.14188 -
ACS Chemical Biology Mar 2023Sialic acid recognition and hydrolysis are essential parts of cellular function and pathogen infectivity. Neuraminidases are enzymes that detach sialic acid from...
Sialic acid recognition and hydrolysis are essential parts of cellular function and pathogen infectivity. Neuraminidases are enzymes that detach sialic acid from sialosides, and their inhibition is a prime target for viral infection treatment. The connectivity and type of sialic acid influence the recognition and hydrolysis activity of the many different neuraminidases. The common strategies to evaluate neuraminidase activity, recognition, and inhibition rely on extensive labeling and require a large amount of sialylated glycans. The above limitations make the effort of finding viral inhibitors extremely difficult. We used synthetic sialylated glycans and developed a label-free electrochemical method to show that sialoside structural features lead to selective neuraminidase biosensing. We compared Neu5Ac to Neu5Gc sialosides to evaluate the organism-dependent neuraminidase selectivity-sensitivity relationship. We demonstrated that the type of surface and the glycan monolayer density direct the response to either binding or enzymatic activity. We proved that while the hydrophobic glassy carbon surface increases the interaction with the enzyme hydrophobic interface, the negatively charged interface of the lipoic acid monolayer on gold repels the protein and enables biocatalysis. We showed that the sialoside monolayers can serve as tools to evaluate the inhibition of neuraminidases both by biocatalysis and molecular recognition.
Topics: Neuraminidase; N-Acetylneuraminic Acid; Biocatalysis; Sialic Acids; Polysaccharides
PubMed: 36792550
DOI: 10.1021/acschembio.2c00913 -
The Science of the Total Environment Jul 2023Tropical primary forests are being destroyed at an alarming rate and converted for other land uses which is expected to greatly influence soil carbon (C) cycling....
Tropical primary forests are being destroyed at an alarming rate and converted for other land uses which is expected to greatly influence soil carbon (C) cycling. However, our understanding of how tropical forest conversions affect the accumulation of compounds in soil functional C pools remains unclear. Here, we collected soils from primary forests (PF), secondary forests (SF), oil-palm (OP), and rubber plantations (RP), and assessed the accumulation of plant- and microbial-derived compounds within soil organic carbon (SOC), particulate (POC) and mineral-associated (MAOC) organic C. PF conversion to RP greatly decreased SOC, POC, and MAOC concentrations, whereas conversion to SF increased POC concentrations and decreased MAOC concentrations, and conversion to OP only increased POC concentrations. PF conversion to RP decreased lignin concentrations and increased amino sugar concentrations in SOC pools which increased the stability of SOC, whereas conversion to SF only increased the lignin concentrations in POC, and conversion to OP just increased lignin concentrations in POC and decreased it in MAOC. We observed divergent dynamics of amino sugars (decrease) and lignin (increase) in SOC with increasing SOC. Only lignin concentrations increased in POC with increasing POC and amino sugars concentrations decreased in MAOC with increasing MAOC. Conversion to RP significantly decreased soil enzyme activities and microbial biomasses. Lignin accumulation was associated with microbial properties, whereas amino sugar accumulation was mainly associated with soil nutrients and stoichiometries. These results suggest that the divergent accumulation of plant- and microbial-derived C in SOC was delivered by the distribution and original composition of functional C pools under forest conversions. Forest conversions changed the formation and stabilization processes of SOC in the long run which was associated with converted plantations and management. The important roles of soil nutrients and stoichiometry also provide a natural-based solution to enhance SOC sequestration via nutrient management in tropical forests.
Topics: Soil; Carbon; Lignin; Forests; Biomass; Rubber
PubMed: 37044342
DOI: 10.1016/j.scitotenv.2023.163204 -
Expert Opinion on Therapeutic Patents Mar 2023Leishmaniasis is an important disease caused by parasites of the Leishmania. Due to the urgent need for financial incentives and research and development of new... (Review)
Review
INTRODUCTION
Leishmaniasis is an important disease caused by parasites of the Leishmania. Due to the urgent need for financial incentives and research and development of new anti-Leishmania, a point that stands out is the creation of patents that comprise drugs and nanoformulations in treating the disease.
AREAS COVERED
Information on individual patents and patent families containing potential drugs and nanoformulations were obtained by searching the Orbit software (QUESTEL SAS, France) using the following terms: Leishmania; treatment; nanoparticle*; drug×. The data obtained ranged from 2015 to 2022.
EXPERT OPINION
Meglumine antimoniate is a pentavalent antimonial widely used in the classic treatment of leishmaniasis. It is part of the classic treatment recommended by WHO, being the first-choice drug globally about 75 years ago. Thus, the need to introduce new anti-Leishmania therapies into clinical medicine is evident since cases of resistance to monotherapy and multitherapy have increased greatly. Associated with this, the search for patents that are good candidates in treating this disease assues interest in investments of financial resources and raises a ray of hope for safe, effective, and low-cost therapies to become licensed for the treatment of leishmaniasis.
Topics: Humans; Antiprotozoal Agents; Patents as Topic; Leishmaniasis; Meglumine Antimoniate; Leishmania
PubMed: 37038719
DOI: 10.1080/13543776.2023.2201431 -
Chemical Record (New York, N.Y.) Nov 2021Sialic acid is an important component of cell surface glycans, which are responsible for many vital body functions and should therefore be thoroughly studied to... (Review)
Review
Sialic acid is an important component of cell surface glycans, which are responsible for many vital body functions and should therefore be thoroughly studied to understand their biological roles and association with disorders. The difficulty of isolating large quantities of homogenous-state sialoglycans from natural sources has inspired the development of the corresponding chemical synthesis methods affording acceptable purities, yields, and amounts. However, the related syntheses are challenging because of the difficulties in α-glycosylation of sialic acid, which arises from its certain structural features such as the absence of a stereodirecting group at the C3 position and presence of carboxyl group at the anomeric position. Moreover, the structural complexities of sialoglycans with diverse numbers and locations of sialic acid on the glycan chains pose additional barriers. Thus, efficient α-stereoselective routes to sialosides remain highly sought after, although various types of sialyl donors/acceptors have been developed for the straightforward synthesis of α-sialosides. Herein, we review the latest progress in the α-stereoselective synthesis of sialosides and their applications in the preparation of gangliosides and other sialoglycans.
Topics: Gangliosides; Glycosylation; N-Acetylneuraminic Acid; Polysaccharides
PubMed: 34028159
DOI: 10.1002/tcr.202100080 -
Cells Feb 2022Unresolved hyperglycaemia, a hallmark of type 2 diabetes mellitus (T2DM), is a well characterised manifestation of altered fuel homeostasis and our understanding of its... (Review)
Review
Unresolved hyperglycaemia, a hallmark of type 2 diabetes mellitus (T2DM), is a well characterised manifestation of altered fuel homeostasis and our understanding of its role in the pathologic activation of the inflammatory system continues to grow. Metabolic disorders like T2DM trigger changes in the regulation of key cellular processes such as cell trafficking and proliferation, and manifest as chronic inflammatory disorders with severe long-term consequences. Activation of inflammatory pathways has recently emerged as a critical link between T2DM and inflammation. A substantial body of evidence has suggested that this is due in part to increased flux through the hexosamine biosynthetic pathway (HBP). The HBP, a unique nutrient-sensing metabolic pathway, produces the activated amino sugar UDP-GlcNAc which is a critical substrate for protein -GlcNAcylation, a dynamic, reversible post-translational glycosylation of serine and threonine residues in target proteins. Protein -GlcNAcylation impacts a range of cellular processes, including inflammation, metabolism, trafficking, and cytoskeletal organisation. As increased HBP flux culminates in increased protein -GlcNAcylation, we propose that targeting -GlcNAcylation may be a viable therapeutic strategy for the prevention and management of glucose-dependent pathologies with inflammatory components.
Topics: Diabetes Mellitus, Type 2; Glycosylation; Hexosamines; Humans; Inflammation; Protein Processing, Post-Translational; Proteins
PubMed: 35203353
DOI: 10.3390/cells11040705 -
Molecular Microbiology Feb 2022N-acetylglucosamine (GlcNAc), an important amino sugar at the infection sites of the fungal pathogen Candida albicans, triggers multiple cellular processes. GlcNAc...
N-acetylglucosamine (GlcNAc), an important amino sugar at the infection sites of the fungal pathogen Candida albicans, triggers multiple cellular processes. GlcNAc import at the cell surface is mediated by GlcNAc transporter, Ngt1 which seems to play a critical role during GlcNAc signaling. We have investigated the Ngt1 dynamics that provide a platform for further studies aimed at understanding the mechanistic insights of regulating process(es) in C. albicans. The expression of this transporter is prolific and highly sensitive to even very low levels (˂2 µM) of GlcNAc. Under these conditions, Ngt1 undergoes phosphorylation-associated ubiquitylation as a code for internalization. This ubiquitylation process involves the triggering proteins like protein kinase Snf1, arrestin-related trafficking adaptors (ART) protein Rod1, and yeast ubiquitin ligase Rsp5. Interestingly, analysis of ∆snf1 and ∆rsp5 mutants revealed that while Rsp5 is promoting the endosomal trafficking of Ngt1-GFPɤ, Snf1 hinders the process. Furthermore, colocalization experiments of Ngt1 with Vps17 (an endosomal marker), Sec7 (a trans-Golgi marker), and a vacuolar marker revealed the fate of Ngt1 during sugar-responsive endosomal trafficking. ∆ras1 and ∆ubi4 mutants showed decreased ubiquitylation and delayed endocytosis of Ngt1. According to our knowledge, this is the first report which illustrates the mechanistic insights that are responsible for endosomal trafficking of a GlcNAc transporter in an eukaryotic organism.
Topics: Acetylglucosamine; Candida albicans; Endocytosis; Endosomal Sorting Complexes Required for Transport; Fungal Proteins; Gene Expression Regulation, Fungal; Phosphoenolpyruvate Sugar Phosphotransferase System; Sugars
PubMed: 34877729
DOI: 10.1111/mmi.14857