Year: 2022

A group from Joint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA, etc. has reported that the innate immune lectin galectin-7 (Gal-7) binds a variety of distinct microbes, all of which share features of blood group-like antigens.
<a href=”https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218387/”>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218387/</a>

It has been known that several members of the galectin family, including galectin-3 (Gal-3), galectin-4 (Gal-4), and galectin-8 (Gal-8), possess the ability to bind blood group A and B with high affinity. Although prior studies demonstrated that Gal-3, Gal-4, and Gal-8 are capable of binding and killing microbes that utilize blood group-like molecular mimicry, the extent to which other members of the galectin family likewise share the ability to provide innate immunity against molecular mimicry remains incompletely defined.

In this report, it was demonstrated that Gal-7 also possesses the ability to bind and kill microbes that utilize blood group molecular mimicry. However, unlike Gal-3, Gal-4, and Gal-8, Gal-7 exhibits very little affinity for mammalian A and B antigens. Despite this, Gal-7 exhibited high specificity toward multiple microbes that express glycans with blood group-like features. These results demonstrate that antimicrobial activity among galectin family members is not limited to Gal-3, Gal-4, and Gal-8, but that Gal-7 likewise possesses the ability to bind and kill microbes expressing blood group-like antigens.

From microarray studies using CFG glycan arrays, at 0.04 μM, Gal-7 engaged only three glycan structures out of nearly 600, a <strong>type 2 (Galβ1-4GlcNAc) blood group A</strong> structure, and two <strong>polylactosamine (polyLacNAc, i blood group)</strong> containing structures capped with the H antigen. At 3.3 μM Gal-7 exhibited binding toward additional glycans, including several glycans containing the blood group B antigen. At 10 μM, Gal-7 is bound to a common non-blood group containing glycans recognized by other galectin family members, including biantennary N-glycans and those with poly-N-acetyllactosamine (polyLacNAc) structures. The selective binding specificity of Gal-7 over a broad range of concentrations distinguishes it from prior reports on other galectins and suggests that unlike Gal-3, Gal-4, and Gal-8, Gal-7 may not readily engage blood group positive microbes.

Although the mechanism whereby Gal-7 and other galectins kill microbes is unclear, the results of this study suggest that an ancient carbohydrate binding protein family expressed in mammals exists that can target a variety of microbes, each of which utilize features of blood-group molecular mimicry.

A group from Centre for Plant Protection and Biotechnology from Valencian Institute of Agricultural Sciences (IVIA), Moncada, València, Spain, etc. has reported about potentially host-beneficial microbes for Citrus.
https://www.sciencedirect.com/science/article/pii/S1871678422000395?via%3Dihub

The citrus microbiota was dominated by either the genera Pseudomonas (ranging from 4.0 % to 20.3 %), by the yet uncultured candidate orders WD2101 (2.2–6.4 %) and iii1–15 (2.4–6.1 %), or by the genera Streptomyces (0.5–4.7 %).
The next most abundant phylotypes were from the families Pirellulaceae (1.9–3.5 %) and Rhizobiaceae (1.1–3.3 %).
After these phylotypes, the families Cytophagaceae and Pseudomadaceae and the genera Sphingomonas and Pirellula represented from 0.4 % to 2.4 % of the total rhizospheric bacterial community associated with citrus trees.

This information allowed selection of potentially host-beneficial bacteria to mine for agricultural probiotics in future biotechnological applications required for the citrus industry.

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.