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The severity assessment of COVID-19 and transmissibility of newly emerged novel-Coronavirus (2019-nCoV) can effectively help and support to quantify the ongoing pandemic risks. Among several epidemiological measures against COVID-19 severity, the case fatality risk (CFR) assessment is an important measure to track record the overall proportion/ratio of the cumulative number of infected patients with the known outcome (confirmed, recovered, or deceased). Considering the ongoing fatality rate, several case-based preventive measures, Coronavirus protein visualization, and approaches to viral vaccine development are discussed herein. The prompt identification of high-risk entities to confront the uncertainty in the risk of death using the approaches highlighted, herein, is of utmost requirement to tackle the current COVID-19 severity. Moreover, the protein visualization available at the viral surface/ body can give further insight into the appropriate vaccine development.

Coagulase-positive Staphylococci (CoPS) can exist as commensals in humans, companion and food-producing animals, but can cause severe or even lethal diseases. Exchange of these bacteria between humans and animals has been described. Special attention has been focused on Methicillin-Resistant Staphylococcus aureus, but other CoPS can also represent an important threat. In addition to significant antimicrobial resistance, these bacteria may carry a plethora of virulence factors - molecules that allow bacteria to establish on or within a host and increase their ability to cause disease. These virulence factors have been widely described in S. aureus but information about other species of CoPS is scarce. The aim of this paper is to review the recent literature about the virulence factors of non-aureus CoPS of animal origin. Their possible effects on human health are also described. The role and prevalence of different virulence factors including leukocidins, hemolysins, adhesins, enterotoxins, exfoliative and toxic shock syndrome toxins as well as superantigen-like proteins are addressed. The effect of these virulence factors on human health is also described. The possibility of misdiagnosis of species of CoPS has been demonstrated in human clinical samples. Prevalence of zoonotic infections could be higher than thought and medical laboratories should be aware of these other staphylococcal species. In keeping with the ‘One Health’ approach to animal and human disease, medical professionals, veterinarians and health workers should be aware of the risks derived from exposure to these bacteria in people in close contact with animals, including pet owners, farmers and veterinarians themselves.

Abstract Extracellular vesicles (EVs) are lipid bilayer‐enclosed nanosized particles released by all cell types during physiological as well as pathophysiological processes to carry out diverse biological functions, including acting as sources of cellular dumping, signalosomes and mineralisation nanoreactors. The ability of EVs to perform specific biological functions is due to their biochemical machinery. Among the components of the EVs’ biochemical machinery, surface proteins are of critical functional significance as they mediate the interactions of EVs with components of the extracellular milieu, the extracellular matrix and neighbouring cells. Surface proteins are thought to be native, that is, pre‐assembled on the EVs’ surface by the parent cells before the vesicles are released. However, numerous pieces of evidence have suggested that soluble proteins are acquired by the EVs’ surface from the extracellular milieu and further modulate the biological functions of EVs during innate and adaptive immune responses, autoimmune disorders, complement activation, coagulation, viral infection and biomineralisation. Herein, we will describe the methods currently used to identify the EVs’ surface proteins and discuss recent knowledge on the functional relevance of the soluble proteins acquired by EVs.

Abstract Background Although Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed. Methods Ninety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR. Results The serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene. 21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele. Conclusions The presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections. This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.

Leptospira, a zoonotic pathogen, is known to infect various hosts and can establish persistent infection. This remarkable ability of bacteria is attributed to its potential to modulate (activate or evade) the host immune response by exploiting its surface proteins. We have identified and characterized the domain of the variable region of Leptospira immunoglobulin-like protein A (LAV) involved in immune modulation. The 11th domain (A11) of the variable region of LigA (LAV) induces a strong TLR4 dependent innate response leading to subsequent induction of humoral and cellular immune responses in mice. A11 is also involved in acquiring complement regulator FH and binds to host protease Plasminogen (PLG), there by mediating functional activity to escape from complement-mediated killing. The deletion of A11 domain significantly impaired TLR4 signaling and subsequent reduction in the innate and adaptive immune response. It also inhibited the binding of FH and PLG thereby mediating killing of bacteria. Our study discovered an unprecedented role of LAV as a nuclease capable of degrading Neutrophil Extracellular Traps (NETs). This nuclease activity was primarily mediated by A11. These results highlighted the moonlighting function of LigA and demonstrated that a single domain of a surface protein is involved in modulating the host innate immune defenses, which might allow the persistence of Leptospira in different hosts for a long term without clearance.

Abstract The extracellular vesicle (EV) surface proteome (surfaceome) acts as a fundamental signalling gateway by bridging intra‐ and extracellular signalling networks, dictates EVs’ capacity to communicate and interact with their environment, and is a source of potential disease biomarkers and therapeutic targets. However, our understanding of surface protein composition of large EVs (L‐EVs, 100–800 nm, mean 310 nm, ATP5F1A, ATP5F1B, DHX9, GOT2, HSPA5, HSPD1, MDH2, STOML2), a major EV‐subtype that are distinct from small EVs (S‐EVs, 30–150 nm, mean 110 nm, CD44, CD63, CD81, CD82, CD9, PDCD6IP, SDCBP, TSG101) remains limited. Using a membrane impermeant derivative of biotin to capture surface proteins coupled to mass spectrometry analysis, we show that out of 4143 proteins identified in density‐gradient purified L‐EVs (1.07–1.11 g/mL, from multiple cancer cell lines), 961 proteins are surface accessible. The surface molecular diversity of L‐EVs include (i) bona fide plasma membrane anchored proteins (cluster of differentiation, transporters, receptors and GPI anchored proteins implicated in cell‐cell and cell‐ECM interactions); and (ii) membrane surface‐associated proteins (that are released by divalent ion chelator EDTA) implicated in actin cytoskeleton regulation, junction organization, glycolysis and platelet activation. Ligand‐receptor analysis of L‐EV surfaceome (e.g., ITGAV/ITGB1) uncovered interactome spanning 172 experimentally verified cognate binding partners (e.g., ANGPTL3, PLG, and VTN) with highest tissue enrichment for liver. Assessment of biotin inaccessible L‐EV proteome revealed enrichment for proteins belonging to COPI/II‐coated ER/Golgi‐derived vesicles and mitochondria. Additionally, despite common surface proteins identified in L‐EVs and S‐EVs, our data reveals surfaceome heterogeneity between the two EV‐subtype. Collectively, our study provides critical insights into diverse proteins operating at the interactive platform of L‐EVs and molecular leads for future studies seeking to decipher L‐EV heterogeneity and function.

Human milk oligosaccharides (HMOs) promote the growth and adhesion of bifidobacteria, thus exerting multiple biological functions on intestinal epithelial cells. Bacterial surface proteins play an important role in bacterial-host intestinal epithelial interactions. In this study, we aim to investigate the effects of surface proteins extracted from Bifidobacterium bifidum DNG6 (B. bifidum DNG6) consuming 2'-fucosyllactose (2'-FL) on Caco-2 cells monolayer barrier injury induced by lipopolysaccharide, compared with lactose (Lac) and galacto-oligosaccharides (GOS). Our results indicated that 2'-FL may promote the surface proteins of B. bifidum DNG6 to improve intestinal barrier injury by positively regulating the NF-κB signaling pathway, reducing inflammation(TNF-α reduced to 50.34%, IL-6 reduced to 22.83%, IL-1β reduced to 37.91%, and IL-10 increased to 63.47%)and strengthening tight junction (ZO-1 2.39 times, Claudin-1 2.79 times, and Occludin 4.70 times). The findings of this study indicate that 2'-FL can further regulate intestinal barrier damage by promoting the alteration of B. bifidum DNG6 surface protein. The findings of this research will also provide theoretical support for the development of synbiotic formulations., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. This protozoan developed several mechanisms to infect, propagate, and survive in different hosts. The specific expression of proteins is responsible for morphological and metabolic changes in different parasite stages along the parasite life cycle. The virulence strategies at the cellular and molecular levels consist of molecules responsible for mediating resistance mechanisms to oxidative damage, cellular invasion, and immune evasion, performed mainly by surface proteins. Since parasite surface coat remodeling is crucial to invasion and infectivity, surface proteins are essential virulence elements. Understanding the factors involved in these processes improves the knowledge of parasite pathogenesis. Genome sequencing has opened the door to high-throughput technologies, allowing us to obtain a deeper understanding of gene reprogramming along the parasite life cycle and identify critical molecules for survival. This review therefore focuses on proteins regulated during differentiation into infective forms considered virulence factors and addresses the current known mechanisms acting in the modulation of gene expression, emphasizing mRNA signals, regulatory factors, and protein complexes.

Streptococcus thermophilus, a food grade bacterium, is extensively used in the manufacture of fermented products such as yogurt and cheeses. It has been shown that S. thermophilus strains exhibited varying anti-inflammatory activities in vitro. Our previous study displayed that this activity could be partially due to peptide(s) generated by trypsin hydrolysis of the surface proteins of S. thermophilus LMD-9. Surface protease PrtS could be the source of these peptides during gastrointestinal digestion. Therefore, peptide hydrolysates were obtained by shaving two phenotypically distinct strains of S. thermophilus (LMD-9 PrtS+ and CNRZ-21N PrtS−) with pepsin, a gastric protease, followed or not by trypsinolysis. The peptide hydrolysates of both strains exhibited anti-inflammatory action through the modulation of pro-inflammatory mediators in LPS-stimulated THP-1 macrophages (COX-2, Pro-IL-1β, IL-1β, and IL-8) and LPS-stimulated HT-29 cells (IL-8). Therefore, peptides released from either PrtS+ or PrtS− strains in the gastrointestinal tract during digestion of a product containing this bacterium may display anti-inflammatory effects and reduce the risk of inflammation-related chronic diseases.

Chlamydia trachomatis ( C. trachomatis ) is an obligate intracellular bacterium which causes eye and sexually transmitted infections. During pregnancy, the bacterium is associated with preterm complications, low weight of neonates, fetal demise and endometritis leading to infertility. The aim of our study was design of a multi-epitope vaccine (MEV) candidate against C. trachomatis . After protein sequence adoption from the NCBI, potential epitopes toxicity, antigenicity, allergenicity, MHC-I and MHC-II binding, cytotoxic T lymphocytes (CTLs), Helper T lymphocytes (HTLs) and interferon-γ (IFN-γ)- induction were predicted. The adopted epitopes were fused together using appropriate linkers. In the next step, the MEV structural mapping and characterization, three-dimensional (3D) structure homology modeling and refinement were also performed. The MEV candidate interaction with the toll-like receptor 4 (TLR4) was also docked. The immune responses simulation was assessed using the C-IMMSIM server. Molecular dynamic (MD) simulation verified the structural stability of the TLR4-MEV complex. The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach demonstrated the MEV high affinity of binding to the TLR4, MHC-I and MHC-II. The MEV construct was also stable and water soluble and had enough antigenicity and lacked allergenicity with stimulation of T cells and B cells and INF-γ release. The immune simulation confirmed acceptable responses of both the humoral and cellular arms. It is proposed that in vitro and in vivo studies are needed to evaluate the findings of this study.Communicated by Ramaswamy H. Sarma.

Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults. The mortality rate is very high despite different treatments. New therapeutic targets are therefore highly needed. Cell-surface proteins represent attractive targets due to their accessibility, their involvement in essential signaling pathways, and their dysregulated expression in cancer. Moreover, they are potential targets for CAR-based immunotherapy or mRNA vaccine strategies. In this context, we investigated the GBM-associated surfaceome by comparing it to astrocytes cell line surfaceome to identify new specific targets for GBM. For this purpose, biotinylation of cell surface proteins has been carried out in GBM and astrocytes cell lines. Biotinylated proteins were purified on streptavidin beads and analyzed by shotgun proteomics. Cell surface proteins were identified with Cell Surface Proteins Atlas (CSPA) and Gene Ontology enrichment. Among all the surface proteins identified in the different cell lines we have confirmed the expression of 66 of these in patient's glioblastoma using spatial proteomic guided by MALDI-mass spectrometry. Moreover, 87 surface proteins overexpressed or exclusive in GBM cell lines have been identified. Among these, we found 11 specific potential targets for GBM including 5 mutated proteins such as RELL1, CYBA, EGFR, and MHC I proteins. Matching with drugs and clinical trials databases revealed that 7 proteins were druggable and under evaluation, 3 proteins have no known drug interaction yet and none of them are the mutated form of the identified proteins. Taken together, we discovered potential targets for immune therapy strategies in GBM. [ABSTRACT FROM AUTHOR]

The increase in concern from viable cells of probiotics specifically in acute inflammatory conditions has led to the emergence of the concept of postbiotics as a safer alternative therapy in the field of health and wellness. The aim of the present study was to evaluate the efficacy of surface proteins from three probiotic strains in dextran sodium sulfate and trinitrobenzenesulphonic acid = induced colitis mouse models. The molecular weight of total surface proteins extracted from the three probiotic strains ranged from ∼25 to ∼250 kDa with the presence of negligible levels of endotoxins. Surface layer proteins (SLPs) (∼45 kDa) were found to be present only in the Lactobacillus acidophilus NCFM strain. In the in vivo study, significant differences were not observed in the weight loss and general appetite, however, the decrease in colon length was apparent in TNBS colitis control mice. Further, the administration of these surface proteins significantly reversed the histopathological damages induced by the colitogens and improved the overall histological score. The oral ingestion of these surface proteins also led to a decrease in myeloperoxidase activity and TNF-α expression while the IL-10 levels significantly increased for the strain NCFM followed by MTCC 5690 and MTCC 5689. Overall, the present study signifies the ameliorative role of probiotic surface proteins in colitis mice, thereby, offering a potential and safer alternative for the management of inflammatory bowel disorders. [ABSTRACT FROM AUTHOR]

Investigating and understanding the response of microbes to various surfaces requires a versatile parametrisation of the surface, and multiple assays that captures the complexity of the biofilm structures. Here, Staphylococcus aureus biofilm viability, polysaccharide poly-N-acetylglucosamine, and proteins on the cell surface were analysed with agar plate- and well plate-based biofilm formation assays. Biofilms were grown on a set of nanostructured polymeric surfaces, which were thoroughly characterised for their surface chemistry and topography. Surface hydrophobicity, summit density as well as peak and valley structure were found to influence the microbial viability and exopolysaccharide abundance level in the agar plate assay. In the well plate assay, surface chemical parameters had a lesser influence on the viability, but roughness caused by valley structures increased the viability and decreased the exopolysaccharide expression. Surface proteins relating to pathogenicity were affected by the biofilm formation assay. The abundance profile of these proteins correlated clearly with several roughness parameters, especially fine structure parameters in the agar plate assay and lateral roughness in the well plate assay. These results highlight the necessity of describing the material surfaces with a versatile set of different roughness parameters to completely understand what specific features of a surface drive a certain bacterial response.

The increase in concern from viable cells of probiotics specifically in acute inflammatory conditions has led to the emergence of the concept of postbiotics as a safer alternative therapy in the field of health and wellness. The aim of the present study was to evaluate the efficacy of surface proteins from three probiotic strains in dextran sodium sulfate and trinitrobenzenesulphonic acid = induced colitis mouse models. The molecular weight of total surface proteins extracted from the three probiotic strains ranged from ∼25 to ∼250 kDa with the presence of negligible levels of endotoxins. Surface layer proteins (SLPs) (∼45 kDa) were found to be present only in the Lactobacillus acidophilus NCFM strain. In the in vivo study, significant differences were not observed in the weight loss and general appetite, however, the decrease in colon length was apparent in TNBS colitis control mice. Further, the administration of these surface proteins significantly reversed the histopathological damages induced by the colitogens and improved the overall histological score. The oral ingestion of these surface proteins also led to a decrease in myeloperoxidase activity and TNF-α expression while the IL-10 levels significantly increased for the strain NCFM followed by MTCC 5690 and MTCC 5689. Overall, the present study signifies the ameliorative role of probiotic surface proteins in colitis mice, thereby, offering a potential and safer alternative for the management of inflammatory bowel disorders.

Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults. The mortality rate is very high despite different treatments. New therapeutic targets are therefore highly needed. Cell-surface proteins represent attractive targets due to their accessibility, their involvement in essential signaling pathways, and their dysregulated expression in cancer. Moreover, they are potential targets for CAR-based immunotherapy or mRNA vaccine strategies. In this context, we investigated the GBM-associated surfaceome by comparing it to astrocytes cell line surfaceome to identify new specific targets for GBM. For this purpose, biotinylation of cell surface proteins has been carried out in GBM and astrocytes cell lines. Biotinylated proteins were purified on streptavidin beads and analyzed by shotgun proteomics. Cell surface proteins were identified with Cell Surface Proteins Atlas (CSPA) and Gene Ontology enrichment. Among all the surface proteins identified in the different cell lines we have confirmed the expression of 66 of these in patient’s glioblastoma using spatial proteomic guided by MALDI-mass spectrometry. Moreover, 87 surface proteins overexpressed or exclusive in GBM cell lines have been identified. Among these, we found 11 specific potential targets for GBM including 5 mutated proteins such as RELL1, CYBA, EGFR, and MHC I proteins. Matching with drugs and clinical trials databases revealed that 7 proteins were druggable and under evaluation, 3 proteins have no known drug interaction yet and none of them are the mutated form of the identified proteins. Taken together, we discovered potential targets for immune therapy strategies in GBM.

This investigation delineates an exhaustive analysis of the clinical, immunological, and genomic landscapes of hepatitis B virus (HBV) infection across a cohort of 22 verified patients. The demographic analysis unveiled a pronounced male bias (77.27%), with patient ages spanning 20 to 85 years and durations of illness ranging from 10 days to 4 years. Predominant clinical manifestations included fever, fatigue, anorexia, abdominal discomfort, and arthralgia, alongside observed co-morbidities such as chronic renal disorders and hepatocellular carcinoma. Antigenic profiling of the HBV envelope proteins elucidated significant heterogeneity among the infected subjects, particularly highlighted by discordances in the detection capabilities of small and large HBsAg assays, suggesting antigenic diversity. Quantitative assessment of viral loads unveiled a broad spectrum, accompanied by atypical HBeAg reactivity patterns, challenging the reliability of existing serological markers. Correlative studies between viral burden and antigenicity of the envelope proteins unearthed phenomena indicative of diagnostic evasion. Notably, samples demonstrating robust viral replication were paradoxically undetectable by the large HBsAg ELISA kit, advocating for more sophisticated diagnostic methodologies. Genotypic examination of three HBV isolates classified them as genotype D (D2), with phylogenetic alignment to strains from various global origins. Mutational profiling identified pivotal mutations within the basic core promoter and preS2/S1 regions, associated with an augmented risk of hepatocellular carcinoma. Further, mutations discerned in the small HBsAg and RT/overlap regions were recognized as contributors to vaccine and/or diagnostic escape mechanisms. In summation, this scholarly discourse elucidates the intricate interplay of clinical presentations, antigenic diversity, and genomic attributes in HBV infection, accentuating the imperative for ongoing investigative endeavors to refine diagnostic and therapeutic modalities. • The study uncovers diverse HBV envelope proteins among infected individuals, notably in small and large HBsAg assays. • Viral load analysis exposes varied HBeAg reactivity patterns, challenging conventional serological markers. • Genotypic analysis identifies HBV isolates as genotype D, with mutations in critical regions linked to hepatocellular carcinoma risk. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have emerged in the last decades as a cell-to-cell communication mechanism. One of their mechanism of action is the direct delivery of their cargo, composed of bioactive molecules to target cells. Different methods (direct electroporation, cell transfection, chemical transfection) were developed to vehicle therapeutic molecules through EVs. However, most of these techniques presented some limitations such as EV disruption and aggregation. In the present study, we demonstrated that a direct temperature-controlled co-incubation of EVs with defined miRNAs is a stable method to deliver information to target cells without affecting EV constitutive content. We chose serum as an easy and abundant source of EVs applicable to autologous treatment after EV modification. Exogenous cel-miR-39 loaded on serum EVs (SEVs) was taken up by human endothelial cells, demonstrating an adequate miRNA loading efficacy based on the co-incubation method. Moreover, SEVs co-incubation with the angiomiRNA-126 (miR-126) enhanced their angiogenic properties in vitro and in vivo by increasing the capacity to induce capillary-like structure formation of human endothelial cells. MiR-126 loaded EVs were also shown to stimulate mouse endothelial cells to invade Matrigel plugs and create more vessels with respect to the EV naive counterpart. When SEVs were loaded with miR-19b, an anti-angiogenic miRNA, they were able to reduce Vascular endothelial growth factors (VEGF) pro-angiogenic capacity, supporting the selective biological effect mediated by the carried miRNA. Lastly, we identified Annexin A2 (ANXA2) as one of the molecules involved in the exogenous RNA binding to serum EV surface, favoring miRNA delivery to target endothelial cells for potential therapeutic application.

Collagens are the primary structural components of mammalian extracellular matrices. In addition, collagens regulate tissue development, regeneration and host defense through interaction with specific cellular receptors. Their unique triple helix structure, which requires a glycine residue every third amino acid, is the defining structural feature of collagens. There are 28 genetically distinct collagens in humans. In addition, several other unrelated human proteins contain a collagen domain. Gram-positive bacteria of the genera Staphylococcus, Streptococcus, Enterococcus, and Bacillus express cell surface proteins that bind to collagen. These proteins of Gram-positive pathogens are modular proteins that can be classified into different structural families. This review will focus on the different structural families of collagen binding proteins of Gram-positive pathogen. We will describe how these proteins interact with the triple helix in collagens and other host proteins containing a collagenous domain and discuss how these interactions can contribute to the pathogenic processes.

Background: Staphylococcus aureus (S. aureus) is one of the most important pathogens in burn infections colonized in the nose and increase the risk of infections. Methods: Overall, 85 S. aureus isolates were isolated from clinical and nasal hospitalized patients and health care workers (HCWs) in a burn unit and non-burn units in Isfahan from June 2016 and September 2016. Genes encoding penicillin-binding protein 2a (mecA) and adhesive surface proteins, including fibronectin-binding proteins (fnbA, fnbB), fibrinogen binding protein (fib), laminin-binding protein(eno), collagen binding protein (cna), elastin binding protein (ebps), intracellular adhesion operon (icaA and icaD) were detected using PCR method. Results: The rate of methicillin-resistant S. aureus (MRSA) among burn and non-burn isolates were 62% (18/29) and 25% (14/56), respectively. The most prevalent MSCRAMMs genes in burn units were eno (86%) and fib (66%). The most common gene pattern in burn center was icaA+fib+eno. The frequency of icaD, fib and ebpS was higher in clinical samples than nasal samples. No relation was found between the MSCRAMMs genes in the burn unit and non-burn units. Conclusion: The high prevalence of MRSA in burn center can be a new challenge for clinicians. The higher frequency of icaD, fib and ebpS in clinical isolates than nasal isolates may reflect the important role of these genes in colonization and pathogenesis of S. aureus.

Systemic infections with pathogenic or facultative pathogenic bacteria are associated with activation and aggregation of platelets leading to thrombocytopenia and activation of the clotting system. Bacterial proteins leading to platelet activation and aggregation have been identified, and while platelet receptors are recognized, induced signal transduction cascades are still often unknown. In addition to proteinaceous adhesins, pathogenic bacteria such as Staphylococcus aureus and Streptococcus pneumoniae also produce toxins such as pneumolysin and alpha-hemolysin. They bind to cellular receptors or form pores, which can result in disturbance of physiological functions of platelets. Here, we discuss the bacteria-platelet interplay in the context of adhesin–receptor interactions and platelet-activating bacterial proteins, with a main emphasis on S. aureus and S. pneumoniae. More importantly, we summarize recent findings of how S. aureus toxins and the pore-forming toxin pneumolysin of S. pneumoniae interfere with platelet function. Finally, the relevance of platelet dysfunction due to killing by toxins and potential treatment interventions protecting platelets against cell death are summarized.

Background. Invasive Group B Streptococcus (GBS; Streptococcus agalactiae ) remains a leading cause of infant morbidity and mortality. Intrapartum antibiotic prophylaxis (IAP) has been implemented in many countries with a reduction in early-onset disease, but an effective vaccine may further reduce the disease burden. Candidate vaccines targeting capsular polysaccharides and surface proteins are now in clinical trials. Methods. Using whole-genome sequencing and phenotypic antimicrobial susceptibility testing, we characterized sterile-site GBS isolates recovered from Western Australian infants between 2004 and 2020. Characteristics were compared between three time periods: 2004-2008, 2009-2015 and 2016-2020. Results. A total of 135 isolates were identified. The proportion of serotype III (22.7 % in Period 1 to 47.9 % in Period 3, P =0.04) and clonal complex 17 (13.6-39.6 %, P =0.01) isolates increased over time. Overall coverage of vaccines currently being trialled was >95 %. No isolates were penicillin resistant (MIC>0.25 mg l -1 ), but 21.5 % of isolates had reduced penicillin susceptibility (MIC>0.12 mg l -1 ) and penicillin MIC increased significantly over time ( P =0.04). Clindamycin resistance increased over time to 45.8 % in the latest period. Conclusions. Based on comprehensive characterization of invasive infant GBS in Western Australia, we found that coverage for leading capsular polysaccharide and surface protein vaccine candidates was high. The demonstrated changes in serotype and molecular type highlight the need for ongoing surveillance, particularly with regard to future GBS vaccination programmes. The reduced susceptibility to IAP agents over time should inform changes to antibiotic guidelines.

Adhesion to the intestinal mucosa is the prerequisite for bifidobacteria to colonize and exert biological functions, whereas the choice of carbon source affects the ability of bifidobacteria to adhere to and interact with intestinal epithelial cells. However, knowledge about the relationship between human milk oligosaccharide consumption by bifidobacteria and its adhesion is still limited. In this study, we aim to investigate the effect of 2′-fucosyllactose (2′-FL) as the carbon source on the growth and adhesion properties of Bifidobacterium bifidum DNG6, and make comparisons with galactooligosaccharides and glucose. We found that the growth and adhesion properties of B. bifidum DNG6 grown in different carbon sources were varied. The 2′-FL as a carbon source improves the adhesion ability of B. bifidum DNG6. The expression of adhesion-associated genes was significantly higher in B. bifidum DNG6 grown in 2′-FL after incubation with Caco-2 cells compared with that in galactooligosaccharides and glucose. Our results indicated that 2′-FL may promote B. bifidum DNG6 adhesion to Caco-2 cells through high expression of genes encoding adhesion proteins. The findings of this study contribute to a better understanding of the involvement of human milk oligosaccharides in the adhesion of bifidobacteria and further support the potential application of 2′-FL as a prebiotic in infant nutritional supplements. [ABSTRACT FROM AUTHOR]

ABSTRACT Although it is normally an innocuous part of the human skin microbiota, Staphylococcus epidermidis has emerged as a major nosocomial pathogen, and implanted foreign materials are an essential risk factor for the development of an infection. The extraordinary efficiency of S. epidermidis to colonize artificial surfaces is particularly related to the ability to form biofilms. Biofilm formation itself critically depends on stable pathogen binding to extracellular host matrix components, e.g. fibronectin (Fn), covering inserted devices in vast amounts. Extracellular matrix binding protein (Embp) and its subdomains referred to as the F-repeat and the FG-repeat are critical for adherence of S. epidermidis to surface-immobilized Fn. Embp-Fn interactions preferentially occur with surface-bound, but not folded, globular Fn via binding to the F3 domain. High-resolution structure analysis of F- and FG-repeats revealed that both repeats are composed of two tightly connected triple α-helix bundles, exhibiting an elongated but rather rigid structural organization in solution. Both F- and FG-repeat possess Fn-binding capacity via interactions with type III subdomain FN12, involving residues within the C and F β-sheet. FN12 essentially supports stability of the globular Fn state, and thus these findings reasonably explain why Embp-mediated interaction of S. epidermidis necessitates Fn surface immobilization. Thus, Embp employs an uncharacterized bacterial Fn-binding mechanism to promote staphylococcal adherence. IMPORTANCE Staphylococcus epidermidis is a leading pathogen in implant-associated hospital infections. The pathogenesis critically depends on bacterial binding to ECM components, specifically fibronectin (Fn). The cell surface-localized, 1-MDa extracellular matrix binding protein (Embp) is essentially characterized by 10 F- and 40 FG-repeats. These repetitive units, each characterized by two α-helical bundles, organize themselves in a rigid, elongated form. Embp binds preferentially to surface-localized but not soluble Fn, with both F- and FG-repeats being sufficient for Fn binding and resulting bacterial adherence. Binding preferentially involves Fn type III domain, specifically residues of FN12 β-sheets C and F. Both play key role in stabilizing the globular Fn conformation, explaining the necessity of Fn surface immobilization for a subsequent interaction with Embp. In comparison to many other bacterial Fn-binding proteins using the Fn N terminus, Embp employs a previously undescribed mechanism supporting the adhesion of S. epidermidis to surface-immobilized Fn.

ABSTRACT Lipoteichoic acid (LTA) is an abundant polymer of the Gram-positive bacterial cell envelope and is essential for many species. Whereas the exact function of LTA has not been elucidated, loss of LTA in some species affects hydrophobicity, biofilm formation, and cell division. Using a viable LTA-deficient strain of the human oral commensal Streptococcus gordonii, we demonstrated that LTA plays an important role in surface protein presentation. Cell wall fractions derived from the wild-type and LTA-deficient strains of S. gordonii were analyzed using label-free mass spectroscopy. Comparisons showed that the abundances of many proteins differed, including (i) SspA, SspB, and S. gordonii 0707 (SGO_0707) (biofilm formation); (ii) FtsE (cell division); (iii) Pbp1a and Pbp2a (cell wall biosynthesis and remodeling); and (iv) DegP (envelope stress response). These changes in cell surface protein presentation appear to explain our observations of altered cell envelope homeostasis, biofilm formation, and adhesion to eukaryotic cells, without affecting binding and coaggregation with other bacterial species, and provide insight into the phenotypes revealed by the loss of LTA in other species of Gram-positive bacteria. We also characterized the chemical structure of the LTA expressed by S. gordonii. Similarly to Streptococcus suis, S. gordonii produced a complex type I LTA, decorated with multiple d-alanylations and glycosylations. Hence, the S. gordonii LTA appears to orchestrate expression and presentation of cell surface-associated proteins and functions. IMPORTANCE Discovered over a half-century ago, lipoteichoic acid (LTA) is an abundant polymer found on the surface of Gram-positive bacteria. Although LTA is essential for the survival of many Gram-positive species, knowledge of how LTA contributes to bacterial physiology has remained elusive. Recently, LTA-deficient strains have been generated in some Gram-positive species, including the human oral commensal Streptococcus gordonii. The significance of our research is that we utilized an LTA-deficient strain of S. gordonii to address why LTA is physiologically important to Gram-positive bacteria. We demonstrate that in S. gordonii, LTA plays an important role in the presentation of many cell surface-associated proteins, contributing to cell envelope homeostasis, cell-to-cell interactions in biofilms, and adhesion to eukaryotic cells. These data may broadly reflect a physiological role of LTA in Gram-positive bacteria.

ABSTRACT The candidate phyla radiation (CPR) comprises a large monophyletic group of bacterial lineages known almost exclusively based on genomes obtained using cultivation-independent methods. Within the CPR, Gracilibacteria (BD1-5) are particularly poorly understood due to undersampling and the inherent fragmented nature of available genomes. Here, we report the first closed, curated genome of a gracilibacterium from an enrichment experiment inoculated from the Gulf of Mexico and designed to investigate hydrocarbon degradation. The gracilibacterium rose in abundance after the community switched to dominance by Colwellia. Notably, we predict that this gracilibacterium completely lacks glycolysis, the pentose phosphate and Entner-Doudoroff pathways. It appears to acquire pyruvate, acetyl coenzyme A (acetyl-CoA), and oxaloacetate via degradation of externally derived citrate, malate, and amino acids and may use compound interconversion and oxidoreductases to generate and recycle reductive power. The initial genome assembly was fragmented in an unusual gene that is hypervariable within a repeat region. Such extreme local variation is rare but characteristic of genes that confer traits under pressure to diversify within a population. Notably, the four major repeated 9-mer nucleotide sequences all generate a proline-threonine-aspartic acid (PTD) repeat. The genome of an abundant Colwellia psychrerythraea population has a large extracellular protein that also contains the repeated PTD motif. Although we do not know the host for the BD1-5 cell, the high relative abundance of the C. psychrerythraea population and the shared surface protein repeat may indicate an association between these bacteria. IMPORTANCE CPR bacteria are generally predicted to be symbionts due to their extensive biosynthetic deficits. Although monophyletic, they are not monolithic in terms of their lifestyles. The organism described here appears to have evolved an unusual metabolic platform not reliant on glucose or pentose sugars. Its biology appears to be centered around bacterial host-derived compounds and/or cell detritus. Amino acids likely provide building blocks for nucleic acids, peptidoglycan, and protein synthesis. We resolved an unusual repeat region that would be invisible without genome curation. The nucleotide sequence is apparently under strong diversifying selection, but the amino acid sequence is under stabilizing selection. The amino acid repeat also occurs in a surface protein of a coexisting bacterium, suggesting colocation and possibly interdependence.

Streptococcus suis, a major emerging pathogen in swine and humans, expresses immunoglobulin G (IgG)-binding proteins (IBPs), which contribute to the ability of organism to evasion of host immune system. The objective of this study was to identify novel pig IgG (pIgG) and human IgG (hIgG)-binding proteins and characterize the binding regions of enolase from Streptococcus suis serotype 2 (S. suis 2). Here, four pIgG-binding proteins (pIBPs) and five hIgG-binding proteins (hIBPs) were identified from S. suis 2 surface proteins by 2D-Far-western blot assays. All the newly captured proteins were expressed and further confirmed their binding activity to pIgG or hIgG by Far-western blot and dot blot. In addition to previously identified factor H, fibronectin, collagen, fibrinogen, plasminogen and laminin, we also found that both pIgG and hIgG can specifically interact with enolase. Binding assays indicated that interactions of S. suis 2 enolase with pIgG and hIgG is primarily mediated by the enolase C-terminal portion (Enolase-C, a.a. 142–432). We found that hIgG exhibited stronger binding ability to Enolase-C than pIgG. Further analysis of the C-terminal regions of enolase (Enolase-C1 and Enolase-C2) suggested that the C-terminus possessed two different binding domains with distinct host IgG proteins. Strikingly, we confirmed that pIgG interacted with the Enolase-C1 (a.a. 142–271) and hIgG interacted with the Enolase-C2 (a.a. 271–432). These observations of enolase provide interesting insights in the pathogenesis of S. suis infection. [ABSTRACT FROM AUTHOR]

Escherichia coli is primarily known as a commensal colonising the gastrointestinal tract of infants very early in life but some strains being responsible for diarrhoea, which can be especially severe in young children. Intestinal pathogenic E. coli include six pathotypes of diarrhoeagenic E. coli (DEC), namely, the (i) enterotoxigenic E. coli , (ii) enteroaggregative E. coli , (iii) enteropathogenic E. coli , (iv) enterohemorragic E. coli , (v) enteroinvasive E. coli and (vi) diffusely adherent E. coli. Prior to human infection, DEC can be found in natural environments, animal reservoirs, food processing environments and contaminated food matrices. From an ecophysiological point of view, DEC thus deal with very different biotopes and biocoenoses all along the food chain. In this context, this review focuses on the wide range of surface molecular determinants acting as surface colonisation factors (SCFs) in DEC. In the first instance, SCFs can be broadly discriminated into (i) extracellular polysaccharides, (ii) extracellular DNA and (iii) surface proteins. Surface proteins constitute the most diverse group of SCFs broadly discriminated into (i) monomeric SCFs, such as autotransporter (AT) adhesins, inverted ATs, heat-resistant agglutinins or some moonlighting proteins, (ii) oligomeric SCFs, namely, the trimeric ATs and (iii) supramolecular SCFs, including flagella and numerous pili, e.g. the injectisome, type 4 pili, curli chaperone-usher pili or conjugative pili. This review also details the gene regulatory network of these numerous SCFs at the various stages as it occurs from pre-transcriptional to post-translocational levels, which remains to be fully elucidated in many cases. [ABSTRACT FROM AUTHOR]

The severity assessment of COVID-19 and transmissibility of newly emerged novel-Coronavirus (2019-nCoV) can effectively help and support to quantify the ongoing pandemic risks. Among several epidemiological measures against COVID-19 severity, the case fatality risk (CFR) assessment is an important measure to track record the overall proportion/ratio of the cumulative number of infected patients with the known outcome (confirmed, recovered, or deceased). Considering the ongoing fatality rate, several case-based preventive measures, Coronavirus protein visualization, and approaches to viral vaccine development are discussed herein. The prompt identification of high-risk entities to confront the uncertainty in the risk of death using the approaches highlighted, herein, is of utmost requirement to tackle the current COVID-19 severity. Moreover, the protein visualization available at the viral surface/body can give further insight into the appropriate vaccine development. [ABSTRACT FROM AUTHOR]

Teichoic acids (TAs) are the most abundant glycopolymers in the cell wall of Listeria, an opportunistic Gram‐positive pathogen that causes severe foodborne infections. Two different structural classes of Listeria TA exist: the polyribitolphosphate‐based wall teichoic acid (WTA) that is covalently anchored to the peptidoglycan, and the polyglycerolphosphate‐based lipoteichoic acid (LTA) that is tethered to the cytoplasmic membrane. While TA polymers govern many important physiological processes, the diverse glycosylation patterns of WTA result in a high degree of surface variation across the species and serovars of Listeria, which in turn bestows varying effects on fitness, biofilm formation, bacteriophage susceptibility and virulence. We review the advances made over the past two decades, and our current understanding of the relationship between TA structure and function. We describe the various types of TA that have been structurally determined to date, and discuss the genetic determinants known to be involved in TA glycosylation. We elaborate on surface proteins functionally related to TA decoration, as well as the molecular and analytical tools used to probe TAs. We anticipate that the growing knowledge of the Listeria surface chemistry will also be exploited to develop novel diagnostic and therapeutic strategies for this pathogen. [ABSTRACT FROM AUTHOR]

Our previous work showed that using Lactobacillus pentosus HC-2 as a probiotic could improve the growth performance, immune response, gut bacterial diversity and disease resistance of L itopenaeus vannamei. However, the probiotic mechanism had not been fully characterized. In the present study, histology and proteomic analysis were performed to explore the influence of HC-2 surface protein on its probiotic effects on L. vannamei after feeding either the intact surface proteins, the probiotic treated with lithium chloride (LiCl) to remove noncovalently bound surface proteins or no probiotic for four weeks. Histological observation found that feeding with normal HC-2 obviously improved the intestinal histology and enhanced the protective effect against pathogen damage, but feeding with LiCl-treated HC-2 did not improve the intestinal environment. A total of over 2764 peptides and 1118 uniproteins were identified from the L. vannamei midgut; 211 proteins were significantly differentially expressed in the normal HC-2 group compared with the control group; 510 proteins were significantly differentially expressed in the LiCl-treated HC-2 group compared with the control group, and 458 proteins were significantly differentially expressed in the LiCl-treated HC-2 group compared with the normal HC-2 group. GO/KEGG enrichment analysis of the significantly different proteins demonstrated that feeding normal HC-2 mainly induced immune response, metabolic, cell adhesion and cell-cell signaling-related protein upregulation, which contributed to bacterial adhesion and colonization in the midgut to improve the shrimp immune system and growth, but these proteins were suppressed after the shrimp were fed bacteria deprived of surface proteins. Taken together, these results indicate that the surface proteins were indispensable for HC-2 to execute probiotic effects in the shrimp midgut. • Surface protein contributes to the improvement of intestinal histology of shrimp by L. pentosus HC-2. • The surface proteins of L. pentosus HC-2 did significantly influence the protein transcription in the shrimp midgut. • Probiotics mainly induce immune, metabolic, cell adhesion and cell-cell signaling proteins expression in the shrimp midgut. • Surface proteins were indispensable for HC-2 execute probiotic effects in midgut of shrimp. [ABSTRACT FROM AUTHOR]

The microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) are a family of proteins that are defined by the presence of two adjacent IgG-like folded subdomains. These promote binding to ligands by mechanisms that involve major conformational changes exemplified by the binding to fibrinogen by the 'dock-lock-latch' mechanism or to collagen by the 'collagen hug'. Clumping factors A and B are two such MSCRAMMs that have several important roles in the pathogenesis of Staphylococcus aureus infections. MSCRAMM architecture, ligand binding, and roles in infection and colonization are examined with a focus on recent developments with clumping factors. Shear stress mechanical forces trigger interactions between MSCRAMMs and their ligands. MSCRAMMs bound to ligands via the dock-lock-latch or collagen-hug mechanisms can only be separated by very strong forces. Clumping factor A has a crucial role in attachment to the endothelium during endovascular infections. Clumping factor B binding to loricrin is important in early abscess formation as well as in adhesion to corneocytes. MSCRAMMs also bind a plethora of ligands by mechanisms that do not involve dock-lock-latch. [ABSTRACT FROM AUTHOR]

Infections caused by the Gram-positive bacterium Streptococcus pneumoniae have become a major health problem worldwide because of their high morbidity and mortality rates, especially in developing countries. This microorganism colonizes the human upper respiratory tract and becomes pathogenic under certain circumstances, which are not well known. In the interaction with the host, bacterial surface structures and proteins play major roles. To gain knowledge into gradual changes and adaptive mechanisms that this pathogen undergoes from when it enters the host, we mimicked several in vivo situations representing interaction with epithelial and macrophage cells, as well as a condition of presence in blood. Then, we analyzed, in four pneumococcal strains, two major surface structures, the capsule and extracellular vesicles produced by the pneumococci, as well as surface proteins by proteomics, using the “shaving” approach, followed by LC-MS/MS. We found important differences in both surface ultrastructures and proteins among the culture conditions and strains used. Thus, this work provides insights into physiological adaptations of the pneumococcus when it interacts with the host, which may be useful for the design of strategies to combat infections caused by this pathogen.

There is no effective vaccine against Streptococcus uberis mastitis in dairy cows. Objectives of this study were (1) to extract S. uberis surface proteins (SUSP) and determine immunoreactivity in vitro and (2) immunogenicity and efficacy in vivo. SUSP was extracted from S. uberis, and their immunoreactivity was tested by western blot. In total, 26 Jersey dairy cows were randomly divided into four groups. Groups 1, 2, and 3 were vaccinated subcutaneously with 4 mg, 1 mg, and 100 μg of SUSP, respectively, with Freund’s incomplete adjuvant. Group 4 (control) was injected with placebo. S. uberis UT888 was infused into two contralateral quarters of each cow during early lactation. Somatic cell count (SCC), bacteria count in milk, and mastitis were monitored. Our results show that SUSP contains multiple protein bands, that ranged from 10 to 100 kDa. All vaccinates showed an increased anti-SUSP IgG antibody. The SCC of all experimentally infected quarters increased after challenge but slightly decreased after day 3 with no significant difference among groups. Milk bacterial count was significantly (p < 0.05) reduced in high and medium doses vaccinated groups than low and control groups. In conclusion, SUSP vaccine is immunogenic and showed a promising efficacy to control bovine S. uberis mastitis.

Senescence is linked to a wide range of age-associated diseases and physiological declines. Thus, senotherapeutics are emerging to suppress the detrimental effects of senescence either by senomorphics or senolytics. Senomorphics suppress the traits associated with senescence phenotypes, while senolytics aim to clear senescent cells by suppressing their survival and enhancing the apoptotic pathways. The main goal of these approaches is to suppress the proinflammatory senescence-associated secretory phenotype (SASP) and to promote the immune recognition and elimination of senescent cells. One increasingly attractive approach is the targeting of molecules or proteins specifically present on the surface of senescent cells. These proteins may play roles in the maintenance and survival of senescent cells and hence can be targeted for senolysis. In this review, we summarize the recent knowledge regarding senolysis with a focus on novel surface biomarkers of cellular senescence and discuss their emergence as senotherapeutic targets.

Limosilactobacillus reuteri and Lactiplantibacillus plantarum strains, previously isolated from weaned piglets, were considered for the evaluation of their adhesive characteristics. Lactobacilli were treated with LiCl in order to remove the surface protein layer, and probiotic activity was compared with those of untreated strains. The autoaggregation, co-aggregation to E. coli F18+, and adhesive abilities of LiCl-treated Limosilactobacillus reuteri and Lactiplantibacillus plantarum were significantly inhibited (p < 0.05) compared with the respective untreated strain. The hydrophobic and basic phenotypes were observed due to the strong affinity to chloroform and low adherence to ethyl acetate. In particular, L. plantarum showed higher hydrophobicity compared to L. reuteri, which may reflect their different colonizing ability. After treatment with LiCl to remove surface proteins, the adherence capabilities of L. reuteri and L. casei on IPEC-J2 cells decreased significantly (p < 0.001) and L. reuteri adhered more frequently. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that both L. reuteri and L. plantarum had several bands ranging from 20 to 100 kDa. Two-dimensional gel electrophoresis showed an acidic profile of the surface-layer polypeptides for both bacterial strains, and more studies are needed to characterize their profile and functions. The results confirm the pivotal role of surface proteins in the probiotic potential of L. reuteri and L. plantarum.

In a review of the features of the bacterial cells are Corynebacterium structure: characterized by an upper layer, highly organized cell wall, cytoplasmic membrane, cytoplasm, nucleoid. Described in detail the structure of the upper layer containing pili (fimbriae), microcapsule surface proteins - PS-2, DIP1281, 67-72r protein (hemagglutinin), porins, sialidase (neuraminidase). These components are the ability to initiate a serial of Corynebacterium work with the host cell, followed by colonization. It submitted a detailed description of the structure and functions of cell wall structures - cord factor, which is a second barrier permeability; arabinogalactan, peptidoglycan, lipomannan and lipoarabinomannan. The structure and function of the cytoplasmic membrane as the main diffusion barrier cell cytoplasm and the genome of Corynebacterium. Presented different molecular genetic methods for the identification and differentiation of closely related species of Corynebacterium.

Others describe protein families spanning different species/genera including proteins related to the biofilm associated protein BAP of I S. aureus i (Valle et al.), polymer adhesion domain containing proteins (Järvå et al.) and collagen binding proteins (Arora et al.). Keywords: surface proteins; adhesion; biofilm; immune evasion; iron acquisition; pili; S-layer EN surface proteins adhesion biofilm immune evasion iron acquisition pili S-layer 1 3 3 05/25/21 20210521 NES 210521 The surfaces of Gram-positive bacterial cells are decorated with a diverse array of proteins including a large group that are covalently anchored to peptidoglycan by sortases. Surface proteins, adhesion, biofilm, immune evasion, iron acquisition, pili, S-layer. [Extracted from the article]

Objectives: Pneumococcal cell wall (PCW) is an inflammatory component in Streptococcus pneumoniae . The cell surface proteins and the toll-like receptors (TLR) signaling response were investigated in the human lung epithelial (A549) cells inoculated with PCW of different serotypes., Materials and Methods: The presence of genes encoding these proteins was determined using polymerase chain reaction (PCR). The structure of the cell walls was analyzed by proton nuclear magnetic resonance (1H NMR). The A549 cell line was challenged with PCW extracts of different serotypes. RNA from the infected host cells was extracted and tested against a total of 84 genes associated with TLR signaling pathways (TLR 1-6 and 10) using RT2 Profiler PCR Array., Results: Cell surface proteins; ply , lytA , nanA , nanB , and cbpD genes were present in all serotypes. The distribution and structure of surface protein genes suggest behavioral changes in the molecules, contributing to the resilience of the strains to antibiotic treatment., Conclusion: TLR2 showed the highest expression, while serotypes 1, 3, and 5 induced higher TNFα and IL-1α, suggesting to be more immunogenic than the other strains tested., Competing Interests: No potential conflicts of interest were reported by the author(s).

Surface proteins and pili (or pilus) anchored on the Gram-positive bacterial cell wall play a vital role in adhesion, colonization, biofilm formation, and immunomodulation. The pilus consists of building blocks called pilins or pilus subunits. The surface proteins and pilins share some common sequences and structural features. They contain an N-terminal signal sequence and the C-terminal cell wall sorting region, enabling their transportation across the membrane and covalent attachment to the bacterial cell wall, respectively. The transpeptidase enzymes called sortases facilitate the covalent links between the pilins during the pilus assembly and between surface proteins or basal subunits of pili and peptidoglycan-bridge during the cell wall anchoring. Thus, elucidating three-dimensional structures for the surface proteins and pilins at the atomic level is essential for understanding the mechanism of adhesion, pilus assembly, and host interaction. This chapter aims to provide a general protocol for crystal structure determination of surface proteins and pilins anchored on the Gram-positive bacterial cell wall and substrates for sortases. The protocol involves the production of recombinant protein, crystallization, and structure determination by X-ray crystallography technique., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Disease progression among HIV-1–infected individuals varies widely, but the mechanisms underlying this variability remains unknown. Distinct disease outcomes are the consequences of many factors working in concert, including innate and adaptive immune responses, cell-mediated and humoral immunity, and both genetic and phenotypic factors. Current data suggest that these multifaceted aspects in infected individuals should be considered as a whole, rather than as separate unique elements, and that analyses must be performed in greater detail in order to meet the requirements of personalized medicine and guide optimal vaccine design. However, the wide adoption of antiretroviral therapy (ART) influences the implementation of systematic analyses of the HIV-1–infected population. Consequently, fewer data will be available for acquisition in the future, preventing the comprehensive investigations required to elucidate the underpinnings of variability in disease outcome. This review seeks to recapitulate the distinct genotypic and phenotypic features of the immune system, focusing in particular on comparing the surface proteins of immune cells among individuals with different HIV infection outcomes.

Osteoblast differentiation is important for the development of bone and the maintenance of bone density. Propionibacterium freudenreichii is a probiotic with an anti-inflammatory property. The aim of this study was to investigate the enhancement effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoblast differentiation, mineralization, and its signaling pathway. For in vitro and in vivo experiments, human fetal osteoblastic cell line hFOB 1.19 and an ovariectomized rat model were used, respectively. Expression levels of genes and proteins related to osteoblast differentiation and mineralization were measured by real-time polymerase chain reaction (qPCR) and Western blotting, respectively. Alizarin red S staining was performed to measure osteoblast mineralization. Heat-killed MJ2 (hkMJ2)-treated cells showed significantly increased osteoblast differentiation via an increase in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) ratio and significantly increased osteoblast mineralization by stimulating the expression of bone morphogenetic protein 2 and runt-related transcription factor 2. Additionally, oral administration of live or heat-killed MJ2 to ovariectomized rats inhibited osteoporosis-induced bone loss. Specifically, surface proteins isolated from MJ2 promoted osteoblast differentiation and mineralization. In conclusion, MJ2 enhanced osteoblast differentiation and mineralization through the OPG/RANKL signaling pathway and the effective component of MJ2 might be its surface proteins.

Medulloblastoma (MB) is the most common malignant brain tumor in children. Recent advances in molecular technologies allowed to classify MB in 4 major molecular subgroups: WNT, SHH, Group 3 and Group 4. In cancer research, cancer cell lines are important for examining and manipulating molecular and cellular process. However, it is important to know the characteristics of each cancer cell line prior to use, because there are some differences among them, even if they originate from the same cancer type. This study aimed to evaluate the similarities and differences among four human medulloblastoma cell lines, UW402, UW473, DAOY and ONS-76. The medulloblastoma cell lines were analyzed for (1) cell morphology, (2) immunophenotyping by flow cytometry for some specifics surface proteins, (3) expression level of adhesion molecules by RT-qPCR, (4) proliferative potential, (5) cell migration, and (6) in vivo tumorigenic potential. It was observed a relationship between cell growth and CDH1 (E-chaderin) adhesion molecule expression and all MB cell lines showed higher levels of CDH2 (N-chaderin) when compared to other adhesion molecule. ONS-76 showed higher gene expression of CDH5 (VE-chaderin) and higher percentage of CD144/VE-chaderin positive cells when compared to other MB cell lines. All MB cell lines showed low percentage of CD34, CD45, CD31, CD133 positive cells and high percentage of CD44, CD105, CD106 and CD29 positive cells. The DAOY cell line showed the highest migration potential, the ONS-76 cell line showed the highest proliferative potential and only DAOY and ONS-76 cell lines showed tumorigenic potential in vivo. MB cell lines showed functional and molecular differences among them, which it should be considered by the researchers in choosing the most suitable cellular model according to the study proposal. [ABSTRACT FROM AUTHOR]

Our previous work showed that Lactobacillus pentosus HC-2 has high antibacterial and adhesion activity, and as a probiotic could improve the nutrients and immunomodulatory effects in the Litopenaeus vannamei farming. In order to further investigate the influence of HC-2 surface protein on its probiotic effects, the immune and digestion related genes expression and enzymes activities, the colonization numbers of HC-2, and the histologic characteristics were analysis in shrimp hepatopancreas after feeding either the intact surface proteins, the probiotic treated with lithium chloride (LiCl) to remove noncovalently bound surface proteins or no probiotic for four weeks. The results showed that the immune genes expression of lysozyme, proPO, LGBP, Penaeidins-3α, crustin and C-type lectin, the immune enzymes activities of superoxide dismutase, catalase and Alkaline phosphatase, and the digestion enzymes of Trypsin, Lipase and α-Amylase were significantly higher in hepatopancreas of shrimp fed with intact HC-2 than that in shrimp fed with base diet or striped surface proteins HC-2 post feeding and challenge. In addition, the shrimp fed with intact HC-2 leads to the bacteria cells adhesion to hepatopancreas was significantly higher than that in shrimp fed with no surface proteins HC-2. Furthermore, the tissue damages of hepatopancreas caused by pathogenic vibrio were obviously observed in shrimp fed with base diet or no surface proteins HC-2, but no signs of damages were found in shrimp fed with intact HC-2. These results demonstrate that surface proteins are important components for HC-2 to execute probiotic effect that improve hepatopancreas immune response and nutrition digestion to protect shrimp against pathogen damage. • Intact L. pentosus HC-2 could protect the shrimp hepatopancreas against pathogen damage. • Surface proteins contribute to L. pentosus HC-2 improving shrimp hepatopancreas immune response. • Surface proteins play a vital role in L. pentosus HC-2 adhesion and colonization in hepatopancreas. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) exert a strong antagonistic activity against many microorganisms including food spoilage organisms and may be used as an alternative to control biofilm formation of pathogens in food industries. The objective of this work was to investigate the ability of fifteen Salmonella strains isolated from poultry environment to form biofilms on different surfaces. In addition, the effect of Lactobacillus kefiri strains 8321 and 83113 and Lactobacillus plantarum 83114 and their surface proteins on biofilm development of Salmonella Enteritidis 115 was studied. The relationship between surface properties of bacteria (hydrophobicity, autoaggregation and coaggregation with lactobacilli) and biofilm formation was also investigated. Most of Salmonella strains were hydrophilic and five strains were moderately hydrophobic. In general, Salmonella strains showed high aggregation abilities (27–54%). S. Enteritidis 106 and S. Typhimurium 102 and 108 showed the highest percentages of autoaggregation. All Salmonella strains tested showed aggregation abilities with the three lactobacilli studied, but the percentage of coaggregation proved to be strain-specific. When comparing stainless steel, glass and polystyrene surfaces, higher levels of biofilm formation occurred on polystyrene plate than on glass surfaces or stainless steel. S. Enteritidis 115 exhibited the greatest attachment to polyestyrene surface. The preincubation or coincubation with the three lactobacilli strains significantly reduced (about 1 log CFU/ml of reduction) the ability of S. Enteritidis 115 to form biofilm compared to the control without lactobacilli. These results were confirmed by confocal microscopy. In the same way, when surface proteins extracted from lactobacilli strains were preincubated or coincubated with S. Enteritidis 115, biofilm formation of this strain was significantly decreased compared to the control. The results obtained showed that these Lactobacillus strains and their surface proteins can be used as alternatives for control of biofilm formation by Salmonella in the poultry industry. Unlabelled Image • Biofilm formation of Salmonella isolated from poultry was investigated under different conditions. • Three Lactobacillus strains can be excellent candidates to prevent Salmonella biofilm formation. • Surface proteins extracted from lactobacilli strains contribute to the Salmonella biofilm inhibition. [ABSTRACT FROM AUTHOR]

Abstract In order to understand the mediation function of surface proteins in probiotic effects executed by Lactobacillus pentosus HC-2 in midgut of Litopenaeus vannamei, the immune and digestion related enzymes and the transcriptome expression were analyzed after shrimp fed with normal HC-2 or with stripped surface proteins HC-2 by lithium chloride (LiCl) treatment. The results showed that the shrimp fed with normal HC-2 produced much higher immune and digestion related enzymes than the control group or LiCl-treated HC-2 group to defense the Vibrio parahaemolyticus E1 infection. We obtained total over 275,099 unigenes from L. vannamei midgut, 981 genes were significant differentially expressed in normal HC-2 group compared with control, 1314 genes were significant differentially expressed in LiCl-treated HC-2 group compared with control, and 1689 genes were significant differentially expressed in LiCl-treated HC-2 group compared with normal HC-2 group. The GO/KEGG enrichment analysis of the significantly different genes demonstrated that L. vannamei fed with normal HC-2 induced immune-related, signal transduction, ion homeostasis, cell-cell adhesion, response stress/stimulus, vascular endothelial growth factor and peritrophin genes up-regulation, which were important genes involved in improving the shrimp intestine immune response, nutrition and growth performance, and bacteria adhesion and colonization, but these genes were suppressed in the midgut of shrimp fed with deprived surface proteins bacteria. Taken together, these results indicated that the surface proteins were essential for HC-2 executing probiotic effects in midgut of shrimp. Our data contribute to improve the current understanding of host - Lactobacillus interaction and the probiotic mechanisms in shrimps. Highlights • Surface proteins contribute to L. pentosus HC-2 enhancing the immune and digestion related enzymes in shrimp midgut. • The surface proteins of L. pentosus HC-2 did significantly influence the genes transcription in shrimp midgut. • Probiotics mainly induce immune, signal transduction, cell adhesion and stress response genes expression in shrimp midgut. • Surface proteins were indispensable for HC-2 executing probiotic effects in midgut of shrimp. [ABSTRACT FROM AUTHOR]