Category Nature

A group from Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada, etc. has reported that α2,6-Sialylation is upregulated in severe COVID-19.
https://pubmed.ncbi.nlm.nih.gov/35702159/

In influenza, severity of disease was found to be associated with levels of high mannose and the innate immune lectin MBL2. In SARS-CoV-2 infection, antibody glycosylation has been studied as a marker of severity. Antibodies to the spike protein were altered in severe patients, with lower fucosylation and sialylation observed. This has potential consequences for effector function. However, such studies have focused on a single protein type (IgG). To date there has been no work on the systemic glycomic response to SARS-CoV-2 infection in plasma and no analysis of infected tissues.

Herein, high-throughput analysis of plasma and autopsy sample glycosylation was performed from COVID-19 patients using a lectin microarray technology. It was revealed that plasma α2,6-sialic acid could be a marker of severity. This modification is known to increase the half-life of select proteins, including IgG. In plasma, it was found that the fraction of α2,6-sialylated C5 and C9 in severe COVID-19 patients is significantly upregulated. In line with this, it was observed that the staining for complement proteins C5 and C9 in COVID-19 autopsy samples got stronger.

However, the functional significance of sialylation on complement proteins remains poorly understood. Glycosylation can also play a role in controlling both serum half-life and resistance to proteolytic cleavage, which is of particular importance to this cascade. The α2,6-sialylation may be increasing half-life, prolonging the cell-mediated damage from the cascade. There may also be other effects of α2,6-sialylation on complement biology that have yet to be discovered. It will be needed to understand the functional impact of α2,6 sialylation and other glycans on complement.

A group from Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Mohakhali, Dhaka, Bangladesh, etc. has reported that a higher relative abundance of sialylated Human milk oligosaccharides (HMOs) in mothers’ breastmilk may have a negative impact on young infants’ nutritional status.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177541/

HMOs are not digestible by infants and arrive intact to the large intestine, where they exert prebiotic roles by supporting the development of selected beneficial groups of the gut microbiota, including Bifidobacterium sp and some Lactobacillus sp. by providing metabolic products for their existence, growth, and ultimate colonization in the gut of infant. In addition to helping in healthy gut microbiome, HMOs deliver a number of assistances to infants, including brain development, acting as decoys for harmful organism, and averting disease and infection.

Human milk oligosaccharides differ between secretor and non-secretor mothers, whereby fucosylation in the human milk oligosaccharides are a result of gene products that regulate Lewis and secretor blood group types.

In this study, a total of 45 breast milk samples, of which 26 were from the mothers of severe acute malnutrition (SAM) infants and 19 were from mothers of non-malnourished infants. Among the mothers of SAM infants, 14 were secretors and 12 were non-secretors.

It was found that sialylated HMOs were associated with higher odds of severe acute malnutrition status in age and sex adjusted model (AOR = 2.00, 90% CI 1.30, 3.06), in age, sex, secretor status adjusted model (AOR = 1.96, 90% CI 1.29, 2.98) and also among non-secretor mothers when age and sex adjusted model was used (AOR = 2.86, 90% CI 1.07, 7.62). All these different statistical models show statistically significant association with sialylated HMO and severe acute malnutrition among the young infants. Fucosylated HMOs were less likely associated with severe acute malnutrition but there was no significant association between these.

model 1: adjusted odds ratio (aOR) (90% CI) was adjusted for age and sex.
model 2: adjusted odds ratio (aOR) (90% CI) was adjusted for age and sex and secretor status.
model 3: it was for secretor mothers only and adjusted odds ratio (aOR) (90% CI) was adjusted for age and sex.
model 4: it was for non-secretor mothers only and adjusted odds ratio (aOR) (90% CI) was adjusted for age and sex.

A group from Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Centre, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany, etc. has reported about the importance of Galectin-1 in the process of H-1 Parvovirus infection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146882/

Oncolytic viruses selectively infect and destroy cancer cells while sparing normal tissues. They can also stimulate strong anti-tumour immune responses and destroy tumour vasculature. No fewer than 40 oncolytic viruses are currently under evaluation in clinical trials as treatments against a variety of cancers. Among them is H-1 rat protoparvovirus (H-1PV), a member of the Parvoviridae family in the genus Protoparvovirus.

It was found that H-1PV enters cancer cells via clathrin-mediated endocytosis, a process that involves dynamin and requires a low pH in the endocytic compartments. It was also found that laminins, in particular those containing the laminin γ1 chain, act as attachment factors at the cell surface for a successful H-1PV infection. In particular, sialic acid moieties in the laminins provide a docking place for the virus to anchor to at the cell surface, and Gal-1 promotes the efficient internalisation of virus particles into a clathrin-coated pit. After engagement of these factors, H-1PV penetrates the cells preferentially via clathrin-mediated endocytosis.

A group from Department of Medicine, Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA, etc. has reported about unstudied function and diversity of bacterial lectins found in the human intestinal commensal microbiome.
https://www.nature.com/articles/s41467-022-29949-3

One commensal bacterial effector gene (Cbeg) family that was found in commensal intestinal bacteria of multiple patient stool samples is composed of uncharacterized genes predicted to encode for lectins (e.g., Cbeg4 and Cbeg5).

A predicted domain analysis of Cbeg4 and Cbeg5 revealed both genes encode proteins containing a secretion signal peptide, a fibronectin type 3 domain (Fn; IPR003961) and a carbohydrate-binding module domain (CBM, CBM6-CBM35-CBM36_like_2, IPR033803). Among 865 proteins found in the Uniprot database that are predicted to contain a CBM6-CBM35-CBM36_like_2 carbohydrate-binding domain, 108 different domain architectures and only 2 functionally characterized proteins were identified. The two functionally characterized proteins with a CBM6-CBM35-CBM36_like_2 domain are enzymes and not lectins; one is a xanthan lyase isolated from Bacillus sp. GL1 and the other is a golgi trafficking enzyme (golvesin) isolated from Dyctostelium discoideum. Analysis of the Cbeg4 and Cbeg5 protein sequence by SWISS-MODEL suggests Cbeg4 and Cbeg5 exist as monomeric proteins. The domain architecture of Cbeg4 and Cbeg5 is specific to commensal Bacteroides species and is distinct from any functionally characterized lectins.

Glycan structures that bound to either CBM4 or CBM5 share a common Galβ1–3GlcNacβ1–2Manα1–3Man motif. In human glycomics data from the Glyconnect database, this N-linked glycan sub-structure is most frequently seen in datasets generated from peripheral blood mononuclear cells (PBMC). Based on their domain content and glycan-binding properties Cbeg4 and Cbeg5 appear to be lectins that bind leukocyte-associated N-linked glycan motifs.

Actually, for CD14⁺ monocytes, CD16⁺ monocytes, and cDC2 dendritic cells Cbeg5 increased IL-1β, IL-6, IL-8, IL-10 and TNFα in a dose-dependent manner. Cbeg5 also affected cytokine production in CD1c−CD14−CD16−CD11c⁺ myeloid cells (mCD11c). The induction of cytokines in these four cell populations (CD14⁺ monocytes, CD16⁺ monocytes, cDC2 dendritic cells, and mCD11c cells) was striking with a >100-fold increase relative to the PBS control. To date the role of lectins in the human microbiome has focused on their function as adhesins or in the binding and transport of glycans for bacterial metabolism. The functional analysis of Cbeg5 exampled in interaction with PBMCs mentioned above suggests the diversity of lectin functions in the human microbiome may extend to regulation of the mucosal immune system.

Those lectins encoded by human microbiota represent a biologically relevant, functionally diverse, but yet largely unstudied. The systematic investigation of these lectins will improve our understanding of how the human microbiome contributes to health and disease.

A group from Environmental Molecular Sciences Laboratory, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA, etc. has reported about spatial and abundance mapping of plant N-glycosylation cellular heterogeneity inside Soybean Root Nodules.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150855/

Although glycans are significant mediators of the nodulation process and plant-microbe interactions, there are no studies on whether protein N-glycosylation is affected by nitrogen fixation. Therefore, we compared N-glycome spatial and abundance profiles in soybean nodules infected with wild-type rhizobia and infected with nifH-mutant rhizobia incapable of efficiently fixing atmospheric nitrogen. The nifH-mutant still infects the root and forms the nodules, but cannot fix the nitrogen.

It was found that the majority of N-glycans showed an overall higher abundance in the nifH-mutant nodules, only a few N-glycans showed non-significant changes between WT and nifH-nodules, while no N-glycan was found significantly more abundant in WT. Notably, all glycans with Lewis^aN-がた-epitope showed significantly higher abundance in the nifH-mutant nodule tissue. In contrast, the level of truncated N-glycans was conserved between the two types of nodules.

Proteomic results identified nine glycoproteins as potentially major carriers of Lewis^a glycans as possible candidates for further characterization.
The nine proteins identified were as follows; phytocyanin domain-containing protein (I1LWP0), amidohydro-rel domain-containing protein (I1L921), dirigent protein (I1JL51), peroxidase (I1MP39), germin-like protein (C7S8D5), an uncharacterized copper ion binding protein with oxidoreductase activity (I1MUX7), an uncharacterized enzyme with mannosyl-oligosaccharide glucosidase activity (I1K3K7), and two uncharacterized proteins with unknown molecular function (I1K380, and C5HU39).

Glycoproteins with those specific glycans may be involved in mediating efficient biological nitrogen fixation or downstream effects during bacteroid infection. Indeed, all these nine proteins have known or predicted functions related to biological nitrogen fixation or root development, and it is plausible that their Lewis^a-type glycosylation may be involved in their function.

A group from Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON Canada, etc. has reported that P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is expressed on HIV-1 envelops and can mediate virus capture and subsequent transfer to permissive cells (CD4⁺ T-cells etc).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123692/

P-selectin glycoprotein ligand-1 (PSGL-1/CD162) has been studied extensively for its role in mediating leukocyte rolling through interactions with its cognate receptor, P-selectin. Structurally, PSGL-1 is a highly glycosylated homodimeric transmembrane protein, with an extracellular domain (ECD) of 50–60 nm in length that extends far out from the cellular surface.

In reality, PSGL-1 plays diverse roles in the physiology of HIV-1 infection. It has been shown that the viruses with high levels of PSGL-1 are not infectious as show below.

Since the primary target of HIV-1 infection, CD4⁺ T cells, are often found on activated endothelial tissues which display P-selectin in inflammatory conditions, it was interested in testing whether virions captured by P-selectin could be transferred to nearby permissive cells to elicit infection.
It was decided to test this model with T cell line and PBMC viruses, which contained lower levels of PSGL-1 and higher levels of gp120. We observed that viruses produced in T cell lines and primary PBMC were captured by P-selectin at levels that were markedly higher than the control. Most importantly, both viruses were effectively captured by P-selectin and transferred to HIV-1-permissive cells, suggesting that this mechanism of PSGL-1-mediated virus capture and transfer might also occur when HIV viruses encounter P-selectin on cell surfaces in vivo.

A group from Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia, etc. has reported that a lectin with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, inhibits both cysteine and aspartic proteases.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104457/

Sequence-based structural analysis about Coprinopsis cinerea predicted that the two encoded proteins, CCP1 and CCP2, respectively, and their paralog CCP3, containing a Ricin-type β-trefoil lectin-like domain. All three proteins lack a signal peptide for classical secretion and are, thus, predicted to be cytoplasmic.

It was found that cocaprins inhibit plant cysteine proteases belonging to the C1 family with Ki in the low micromolar range, and also inhibit aspartic protease pepsin with Ki in the low micromolar range.

It has shown that cocaprins have lectin activity in addition to protease inhibition. Glycan microarrays were used to analyze carbohydrate binding specificity of cocaprins. For CCP1, very weak binding was observed on a mammalian glycan array to structures including LacNAc or polyLacNAc and for CCP2 the binding was even weaker. This shows a potential for glycan-binding activity in cocaprins.

However, the biological function of cocaprins is unknown. Regarding a potential role in defense, it is noteworthy that CCP2 expression was induced upon challenge with a fungivorous nematode . However, no toxicity of the protein was detected against nematodes or dipteran insect larvae, although all of which have been shown to be targeted by other β-trefoil protease inhibitors and lectins. Strange isn’t it.

A group from Molecular Plant Physiology, Institute of Botany, University of the Punjab, Lahore, Pakistan, etc. has reported about the effects of sulfonamides on soil microbial population and respiration in rhizospheric soil of wheat.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264476

Sulfonamide is widely used in livestock farming and has been used to treat a variety of bacterial diseases. Due to poor management, they are excreted into the soil after treatments and these are extremely hazardous. Sulfonamides may impair the growth of plants, leaves, and roots at concentrations of several hundred mg/L. Accumulations of different antibiotics, including sulfonamides harmed the function and activity of microorganism and reduce soil enzymatic activity. Antibiotics in soil can bring constant changes in organisms and plants and exert harmful impacts on soil microbes.

This study was conducted to infer impact of four newly synthesized sulfonamides on isolated native strains from rhizosphere of wheat cultivar ‘Chakwal-50’. Furthermore, present research focused on the susceptibility of soil microbes and microbial respiration in the rhizospheric soil of wheat.

Sulfonamides: 2-(phenylsulfonyl) hydrazine carbothioamide (TSBS-1), N, 2-bis phenyl hydrazine carbothioamide (TSBS-2), aminocarbonyl benzene sulfonamide (UBS-1), and N, N’-carbonyl dibenzene sulfonamide (UBS-2) were applied on five isolated bacterial strains, i.e., AC (Actinobacter spp), RS-3a (Bacillus spp.), RS-7a (Bacillus subtilis), RS-4a (Enterobacter spp.) and RS-5a (Enterobacter spp.) isolated from the wheat rhizosphere. All sulfonamide derivatives exhibited antibacterial activity against tested bacterial strains, except for TSBS-1. In comparison of all sulfonamide derivatives, UBS-1 exhibited the highest inhibition zone (11.47 ± 0.90 mm) against RS-4a at the highest concentration (4 mg/ml).

numbers in the figure are UBS-1 concentrations (mg/mL)

Thus, sulfonamides have a negative influence on the soil microbiome, and some soil microorganisms that are unable to resist such stressors, so it is difficult to retain soil fertility and plant development as well. Soil microbial respiration changes mediated by sulfonamides were dependent on length of exposure and concentration. It is needed that antibiotics should be carefully watched and their impact on plant growth should be tested in the future studies.