Consortium of 2029 and 7247 Strains Shows In Vitro Bactericidal Effect on and, in Combination with Prebiotic, Protects Against Intestinal Barrier Dysfunction.

(CJ) is the etiological agent of the world's most common intestinal infectious food-borne disease, ranging from mild symptoms to fatal outcomes. The development of innovative synbiotics that inhibit the adhesion and reproduction of multidrug-resistant (MDR) CJ in animals and humans, thereby preserving intestinal homeostasis, is relevant. We have created a synbiotic based on the consortium of 2029 (LC2029), 7247 (LS7247), and a mannan-rich prebiotic (Actigen).

RNA-Binding S1 Domain in Bacterial, Archaeal and Eukaryotic Proteins as One of the Evolutionary Markers of Symbiogenesis.

The RNA-binding S1 domain is a β-barrel with a highly conserved RNA-binding site on its surface. This domain is an important part of the structures of different bacterial, archaeal, and eukaryotic proteins. A distinctive feature of the S1 domain is multiple presences (structural repeats) in proteins and protein complexes.

A Novel Subsp. T1 Strain from Cow's Milk: Homeostatic and Antibacterial Activity against ESBL-Producing .

The global emergence of antibiotic-resistant zooanthroponotic strains, producing extended-spectrum beta-lactamases (ESBL-E) and persisting in the intestines of farm animals, has now led to the development of a pandemic of extra-intestinal infectious diseases in humans. The search for innovative probiotic microorganisms that eliminate ESBL-E from the intestines of humans and animals is relevant. Previously, we received three isolates of bifidobacteria: from milk of a calved cow (BLLT1), feces of a newborn calf (BLLT2) and feces of a three-year-old child who received fresh milk from this calved cow (BLLT3).

In Search for Low-Molecular-Weight Ligands of Human Serum Albumin That Affect Its Affinity for Monomeric Amyloid β Peptide.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer's disease (AD) patients leads to Aβ accumulation and the formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is the reduction of free Aβ levels by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) in HSA to improve its affinity for Aβ.

Recognition of granulocyte-macrophage colony-stimulating factor by specific S100 proteins.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To probe selectivity of these interactions, the affinity of recombinant human GM-CSF to dimeric Ca-loaded forms of 18 recombinant human S100 proteins was studied by surface plasmon resonance spectroscopy.

Anti- Defence and Intestinal Homeostatic Maintenance In Vitro of a Consortium Containing 3872 and s 7247 Strains in Human, Porcine, and Chicken Enterocytes.

strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. strain 7247 (LS7247) was isolated at the same time from the intestines and reproductive system of a healthy woman. The genomes of these strains contain genes responsible for the production of peptidoglycan-degrading enzymes and factors that increase the permeability of the outer membrane of Gram-negative pathogens.

Protective Properties of S-layer Protein 2 from 2029 against Infections.

Previously, the protective role of the S-layer protein 2 (Slp2) of the vaginal 2029 (LC2029) strain against foodborne pathogens , serovar Enteritidis, and O157:H was demonstrated. We demonstrate the new roles of the Slp2-positive LC2029 strain and soluble Slp2 against infections. We show that LC2029 bacteria can adhere to the surface of the cervical epithelial HeLa cells, prevent their contact with , and block yeast transition to a pathogenic hyphal form.

7247 Strain: Probiotic Properties and Anti- Effect with Prebiotics.

The 7247 (LS7247) strain, originally isolated from a healthy woman's intestines and reproductive system, has been studied for its probiotic potential, particularly against Enteritidis (SE) and Typhimurium (ST) as well as its potential use in synbiotics. LS7247 showed high tolerance to gastric and intestinal stress and effectively adhered to human and animal enterocyte monolayers, essential for realizing its probiotic properties. LS7247 showed high anti- activity.

Interaction of S100A6 Protein with the Four-Helical Cytokines.

S100 is a family of over 20 structurally homologous, but functionally diverse regulatory (calcium/zinc)-binding proteins of vertebrates. The involvement of S100 proteins in numerous vital (patho)physiological processes is mediated by their interaction with various (intra/extra)cellular protein partners, including cell surface receptors. Furthermore, recent studies have revealed the ability of specific S100 proteins to modulate cell signaling via direct interaction with cytokines.

3872 That Produces Class III Bacteriocin Forms Co-Aggregates with the Antibiotic-Resistant Strains and Induces Their Lethal Damage.

LF3872 was isolated from the milk of a healthy lactating and breastfeeding woman. Earlier, the genome of LF3872 was sequenced, and a gene encoding unique bacteriocin was discovered. We have shown here that the LF3872 strain produces a novel thermolabile class III bacteriolysin (BLF3872), exhibiting antimicrobial activity against antibiotic-resistant strains.

Heparin-Induced Changes of Vascular Endothelial Growth Factor (VEGF) Structure.

Vascular endothelial growth factor-A (VEGF-A), a secreted homodimeric glycoprotein, is a critical regulator of angiogenesis in normal and pathological states. The binding of heparin (HE) to VEGF (the major form of VEGF-A) modulates the angiogenesis-related cascade, but the mechanism of the observed changes at the structural level is still insufficiently explored. In the present study, we examined the effect of HE on the structural and physicochemical properties of recombinant human VEGF (rhVEGF).

Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro.

Calcium-Bound S100P Protein Is a Promiscuous Binding Partner of the Four-Helical Cytokines.

S100 proteins are multifunctional calcium-binding proteins of vertebrates that act intracellularly, extracellularly, or both, and are engaged in the progression of many socially significant diseases. Their extracellular action is typically mediated by the recognition of specific receptor proteins. Recent studies indicate the ability of some S100 proteins to affect cytokine signaling through direct interaction with cytokines.

Ibuprofen Favors Binding of Amyloid-β Peptide to Its Depot, Serum Albumin.

The deposition of amyloid-β peptide (Aβ) in the brain is a critical event in the progression of Alzheimer's disease (AD). This Aβ deposition could be prevented by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). Previously, we revealed that specific endogenous ligands of HSA improve its affinity to monomeric Aβ.

Interferon-β Activity Is Affected by S100B Protein.

Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca-binding proteins possessing cytokine-like activities (Int J Mol Sci.

Erythropoietin Interacts with Specific S100 Proteins.

Erythropoietin (EPO) is a clinically significant four-helical cytokine, exhibiting erythropoietic, cytoprotective, immunomodulatory, and cancer-promoting activities. Despite vast knowledge on its signaling pathways and physiological effects, extracellular factors regulating EPO activity remain underexplored. Here we show by surface plasmon resonance spectroscopy, that among eighteen members of Ca-binding proteins of the S100 protein family studied, only S100A2, S100A6 and S100P proteins specifically recognize EPO with equilibrium dissociation constants ranging from 81 nM to 0.

Serotonin Promotes Serum Albumin Interaction with the Monomeric Amyloid β Peptide.

Prevention of amyloid β peptide (Aβ) deposition via facilitation of Aβ binding to its natural depot, human serum albumin (HSA), is a promising approach to preclude Alzheimer's disease (AD) onset and progression. Previously, we demonstrated the ability of natural HSA ligands, fatty acids, to improve the affinity of this protein to monomeric Aβ by a factor of 3 (BBRC, 510(2), 248-253). Using plasmon resonance spectroscopy, we show here that another HSA ligand related to AD pathogenesis, serotonin (SRO), increases the affinity of the Aβ monomer to HSA by a factor of 7/17 for Aβ/Aβ, respectively.

Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins.

Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633-639).

Highly specific interaction of monomeric S100P protein with interferon beta.

S100 proteins are EF-hand calcium-binding proteins of vertebrates exerting numerous intra- and extracellular actions and involved into multiple diseases. Some of S100 proteins serve as extracellular damage signals via interaction with receptors. Although several S100 proteins directly bind specific cytokines, this phenomenon remains underexplored.

Investigation of the Relationship between the S1 Domain and Its Molecular Functions Derived from Studies of the Tertiary Structure.

S1 domain, a structural variant of one of the "oldest" OB-folds (oligonucleotide/oligosaccharide-binding fold), is widespread in various proteins in three domains of life: Bacteria, Eukaryotes, and Archaea. In this study, it was shown that S1 domains of bacterial, eukaryotic, and archaeal proteins have a low percentage of identity, which indicates the uniqueness of the scaffold and is associated with protein functions. Assessment of the predisposition of tertiary flexibility of S1 domains using computational and statistical tools showed similar structural features and revealed functional flexible regions that are potentially involved in the interaction of natural binding partners.

The number of domains in the ribosomal protein S1 as a hallmark of the phylogenetic grouping of bacteria.

The family of ribosomal proteins S1 contains about 20% of all bacterial proteins including the S1 domain. An important feature of this family is multiple copies of structural domains in bacteria, the number of which changes in a strictly limited range from one to six. In this study, the automated exhaustive analysis of 1453 sequences of S1 allowed us to demonstrate that the number of domains in S1 is a distinctive characteristic for phylogenetic bacterial grouping in main phyla.

Repeats in S1 Proteins: Flexibility and Tendency for Intrinsic Disorder.

An important feature of ribosomal S1 proteins is multiple copies of structural domains in bacteria, the number of which changes in a strictly limited range from one to six. For S1 proteins, little is known about the contribution of flexible regions to protein domain function. We exhaustively studied a tendency for intrinsic disorder and flexibility within and between structural domains for all available UniProt S1 sequences.

Does Intrinsic Disorder in Proteins Favor Their Interaction with Lipids?

Intrinsically disordered proteins (IDPs) are implicated in a range of human diseases, some of which are associated with the ability to bind to lipids. Although the presence of solvent-exposed hydrophobic regions in IDPs should favor their interactions with low-molecular-weight hydrophobic/amphiphilic compounds, this hypothesis has not been systematically explored as of yet. In this study, the analysis of the DisProt database with regard to the presence of lipid-binding IDPs (LBIDPs) reveals that they comprise, at least, 15% of DisProt entries.