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Xueting Liu, Liping Zeng, Zhongqiu Zhao, Yang Xie, Shan Wang, Junyan Zhang, Ying He, Zehong Zou, Jianguo Zhang, Ailin Tao
Staphylococcal enterotoxin A is well known as a superantigen and able to be used for cancer immunotherapy. In this study, recombinant Staphylococcal enterotoxin A was genetically conjugated to epidermal growth factor to produce a chimeric protein recombinant Staphylococcal enterotoxin A-epidermal growth factor expressed in Escherichia coli. The recombinant Staphylococcal enterotoxin A-epidermal growth factor protein was purified using Strep-Tactin affinity chromatography and Endotoxin Removal Resin and identified by sodium dodecyl sulfate-polyacrylamide gel electropheresis and liquid chromatography-tandem mass spectrometry analysis...
January 1, 2018: Technology in Cancer Research & Treatment
Anshu Babbar, Andreas Itzek, Dietmar H Pieper, D Patric Nitsche-Schmitz
Streptococcus dysgalactiae subsp. equisimilis (SDSE), belonging to the group C and G streptococci, are human pathogens reported to cause clinical manifestations similar to infections caused by Streptococcus pyogenes. To scrutinize the distribution of gene coding for S. pyogenes virulence factors in SDSE, 255 isolates were collected from humans infected with SDSE in Vellore, a region in southern India, with high incidence of SDSE infections. Initial evaluation indicated SDSE isolates comprising of 82.35% group G and 17...
March 12, 2018: Folia Microbiologica
Jacklyn R Hurst, Katherine J Kasper, Akshay N Sule, John K McCormick
Streptococcus pyogenes is a human-specific and globally prominent bacterial pathogen that despite causing numerous human infections, this bacterium is normally found in an asymptomatic carrier state. This review provides an overview of both bacterial and human factors that likely play an important role in nasopharyngeal colonization and pharyngitis, as well as the development of acute rheumatic fever and rheumatic heart disease. Here we highlight a recently described role for bacterial superantigens in promoting acute nasopharyngeal infection, and discuss how these immune system activating toxins could be crucial to initiate the autoimmune process in rheumatic heart disease...
March 9, 2018: Infection, Genetics and Evolution
Luis J Jara, Gabriela Medina, Miguel A Saavedra
PURPOSE OF REVIEW: To provide an update about the interactions between infections and autoimmune diseases (AIDs), from the molecular perspective to the clinical spectrum and the differentiation between infection and disease activity. RECENT FINDINGS: Any kind of infection may modify the innate and adaptive immune response through the following mechanisms: molecular mimicry, superantigens, epitope spreading and B-cell activation. The consequence is the overproduction of antibodies shared with those found in AIDs...
March 9, 2018: Current Opinion in Rheumatology
Hasan Alghetaa, Amira Mohammed, Muthanna Sultan, Philip Busbee, Angela Murphy, Saurabh Chatterjee, Mitzi Nagarkatti, Prakash Nagarkatti
Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by Staphylococcus aureus that triggers a strong immune response, characterized by cytokine storm, multi-organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB-driven ALI and mortality in mice. We used a dual-exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post-SEB exposure...
March 7, 2018: Journal of Cellular and Molecular Medicine
Nadia Terrazzini, Paola Mantegani, Florian Kern, Claudio Fortis, Anna Mondino, Stefano Caserta
Background: IL-7 promotes the generation, expansion and survival of memory T cells. Previous mouse and human studies showed that IL-7 can support immune cell reconstitution in lymphopenic conditions, expand tumor-reactive T cells for adoptive immunotherapy and enhance effector cytokine expression by autoreactive T cells. Whether pathogen-reactive T cells also benefit from IL-7 exposure remains unknown. Methods: Here we investigated this issue in cultures of peripheral blood mononuclear cells (PBMCs) derived from patients infected with various endemic pathogens...
February 28, 2018: Journal of Infectious Diseases
Katsuhiro Kohno, Saotomo Itoh, Akari Hanai, Takemasa Takii, Toshinobu Fujiwara, Kikuo Onozaki, Tsutomu Tsuji, Shigeaki Hida
Staphylococcal superantigen like 5 (SSL5) is an exotoxin produced by S. aureus and has a strong inhibitory effect on MMP-9 enzymatic activity. However, the mechanism of inhibition remains unclear. We sought to identify the responsible regions of SSL5 for the interaction with MMP-9 by comparing a series of domain swap and deletion mutants of SSL5. Binding analyses revealed that SSL5 had two regions for binding to MMP-9 catalytic domain, β1-3 region (25 SKELKNVTGY RYSKGGKHYL IFDKNRKFTR VQIFGK60 ) in N-terminal half and α4β9 region (138 KELDFKLRQY LIQNFDLYKK FPKDSKIKVI MKD170 ) in C-terminal half...
February 17, 2018: Biochemical and Biophysical Research Communications
Hema Sharma, Debra Smith, Claire E Turner, Laurence Game, Bruno Pichon, Russell Hope, Robert Hill, Angela Kearns, Shiranee Sriskandan
Staphylococcal toxic shock syndrome (TSS) was originally described in menstruating women and linked to TSS toxin 1 (TSST-1)-producing Staphylococcus aureus. Using UK national surveillance data, we ascertained clinical, molecular and superantigenic characteristics of TSS cases. Average annual TSS incidence was 0.07/100,000 population. Patients with nonmenstrual TSS were younger than those with menstrual TSS but had the same mortality rate. Children <16 years of age accounted for 39% of TSS cases, most caused by burns and skin and soft tissue infections...
February 2018: Emerging Infectious Diseases
Zhigang Li, Joseph J Zeppa, Mark A Hancock, John K McCormick, Terence M Doherty, Geoffrey N Hendy, Joaquín Madrenas
Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a Gα11-containing G protein-coupled receptor (GPCR) leading to PLCβ activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the α2 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Chisato Kurisaka, Teruaki Oku, Saotomo Itoh, Tsutomu Tsuji
The staphylococcal superantigen-like proteins (SSLs) exhibit no superantigenic activity but have recently been considered to act as immune suppressors. It was previously reported that SSL5 bound to P-selectin glycoprotein ligand-1 (PSGL-1) and matrix metalloproteinase (MMP)-9, leading to inhibition of leukocyte adhesion and invasion. These interactions were suggested to depend on sialic acid-containing glycans of MMP-9, but the roles of sialic acids in the interaction between SSL5 and MMP-9 are still controversial...
January 12, 2018: Microbiology and Immunology
J de Wit, J E E Totté, F J M van Buchem, S G M A Pasmans
Staphylococcus (S.) aureus plays a role in the pathogenesis of atopic dermatitis (AD), possibly via the expression of various virulence antigens. An altered antibody response towards these antigens might contribute to inflammation. We aimed to provide an overview of the varying prevalences and odds of antibody responses against S. aureus antigens in AD patients. Data were systematically obtained from Embase, Medline, Web of Science, Scopus, Cochrane, PubMed and Google Scholar (up to February 12th 2016). We selected all original observational and experimental studies assessing anti-staphylococcal antibodies in serum of AD patients...
December 16, 2017: British Journal of Dermatology
Juyeun Lee, Nogi Park, Joo Youn Park, Barbara L F Kaplan, Stephen B Pruett, Juw Won Park, Yong Ho Park, Keun Seok Seo
Superantigens (SAgs) produced by Staphylococcus aureus at high concentrations induce proliferation of T cells bearing specific TCR Vβ sequences and massive cytokinemia that cause toxic shock syndrome. However, the biological relevance of SAgs produced at very low concentrations during asymptomatic colonization or chronic infections is not understood. In this study, we demonstrate that suboptimal stimulation of human PBMCs with a low concentration (1 ng/ml) of staphylococcal enterotoxin C1, at which half-maximal T cell proliferation was observed, induced CD8+ CD25+ T cells expressing markers related to regulatory T cells (Tregs), such as IFN-γ, IL-10, TGF-β, FOXP3, CD28, CTLA4, TNFR2, CD45RO, and HLA-DR...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Valéria Cataneli Pereira, Luiza Pinheiro, Adilson Oliveira, Katheryne Benini Martins, Danilo Flávio Moraes Riboli, Maria de Lourdes Ribeiro de Souza da Cunha
Infections with coagulase-negative staphylococci (CoNS) can involve the production of toxins such as superantigens, which contribute to tissue degradation and inflammatory immune responses. The accessory gene regulator (agr) quorum sensing system coordinates the expression of most S. aureus virulence factors. Therefore, the aim of this study was to investigate the expression of these superantigens and the presence of the agr locus in CoNS strains isolated from blood cultures. PCR was used to detect enterotoxin and agr genes and expression was analyzed by RT-PCR...
February 2018: Microbial Pathogenesis
Joan A Geoghegan, Alan D Irvine, Timothy J Foster
Staphylococcus aureus is frequently isolated from the skin of atopic dermatitis (AD) patients during flares. The normal microbiota is disrupted and the diversity of the microorganisms on the skin is reduced. Many species that produce inhibitors of S. aureus growth decline. Strains from S. aureus clonal complex 1 are enriched among AD sufferers whereas the CC30 strains most frequently isolated from nasal carriers in the normal population are much rarer in AD. S. aureus expresses several molecules that contribute to the intensity of symptoms, including δ-toxin which stimulates mast cells, α-toxin which damages keratinocytes, phenol-soluble modulins which stimulate cytokine release by keratinocytes, protein A which triggers inflammatory responses from keratinocytes, superantigens which trigger B cell expansion and cytokine release, and proinflammatory lipoproteins...
December 9, 2017: Trends in Microbiology
Katarina Kulhankova, Kyle J Kinney, Jessica M Stach, Françoise A Gourronc, Isabella M Grumbach, Aloysius J Klingelhutz, Wilmara Salgado-Pabón
Staphylococcus aureus infective endocarditis (IE) is a fast-progressing and tissue destructive infection of the cardiac endothelium. The superantigens (SAgs) toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin C (SEC), and the enterotoxin gene cluster ( egc ) play a novel and essential role in the etiology of S. aureus IE. Recent studies indicate that SAgs act at the infection site to cause tissue pathology and promote vegetation growth. The underlying mechanism of SAg involvement has not been clearly defined...
December 11, 2017: Infection and Immunity
Alsya J Affandi, Sandra C Silva-Cardoso, Samuel Garcia, Emmerik F A Leijten, Tessa S van Kempen, Wioleta Marut, Joel A G van Roon, Timothy R D J Radstake
CXCL4 regulates multiple facets of the immune response and is highly upregulated in various Th17-associated rheumatic diseases. However, whether CXCL4 plays a direct role in the induction of IL-17 production by human CD4+ T cells is currently unclear. Here, we demonstrated that CXCL4 induced human CD4+ T cells to secrete IL-17 that co-expressed IFN-γ and IL-22, and differentiated naïve CD4+ T cells to become Th17-cytokine producing cells. In a co-culture system of human CD4+ T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL-17 production upon triggering by superantigen...
November 29, 2017: European Journal of Immunology
Daniel M Mrochen, Dorothee Grumann, Daniel Schulz, Janine Gumz, Patricia Trübe, Kathleen Pritchett-Corning, Sarah Johnson, Werner Nicklas, Petra Kirsch, Karine Martelet, Jens van den Brandt, Sabine Berg, Barbara M Bröker, Siouxsie Wiles, Silva Holtfreter
We previously reported that laboratory mice from all global vendors are frequently colonized with Staphylococcus aureus (S. aureus). Genotyping of a snap sample of murine S. aureus isolates from Charles River, US, showed that mice were predominantly colonized with methicillin-sensitive CC88 strains. Here, we expanded our view and investigated whether laboratory mice from other global animal facilities are colonized with similar strains or novel S. aureus lineages, and whether the murine S. aureus isolates show features of host adaptation...
November 20, 2017: International Journal of Medical Microbiology: IJMM
Alexei Shir, Shoshana Klein, Idit Sagiv-Barfi, Tamar Geiger, Maya Zigler, Yael Langut, Nufar Edinger, Alexander Levitzki
Superantigens (SAg) are extremely potent bacterial toxins, which evoke a virulent immune response, inducing non-specific T-cell proliferation, rapid cytokine release and lethal toxic shock, for which there is no effective treatment. We previously developed a small molecule, S101, which potently inhibits proliferating T-cells (Sagiv-Barfi et al, Bioorg Med Chem (2010) 18:6404-6413). In a severe mouse model of toxic shock, a single injection of S101 given together with superantigen challenge, rescued 100% of the mice...
November 15, 2017: Journal of Infectious Diseases
Richard P Novick, Geeta Ram
The staphylococcal pathogenicity islands (SaPIs) are highly mobile 15kb genomic islands that carry superantigen genes and other virulence factors and are mobilized by helper phages. Helper phages counteract the SaPI repressor to induce the SaPI replication cycle, resulting in encapsidation in phage like particles, enabling high frequency transfer. The SaPIs split from a protophage lineage in the distant past, have evolved a variety of novel and salient features, and have become an invaluable component of the staphylococcal genome...
August 2017: Current Opinion in Microbiology
Vineet K Singh, Robert P Ring, Vijay Aswani, Mary E Stemper, Jennifer Kislow, Zhan Ye, Sanjay K Shukla
PURPOSE: Staphylococcus aureus is an opportunistic human pathogen that can cause serious infections in humans. A plethora of known and putative virulence factors are produced by staphylococci that collectively orchestrate pathogenesis. Ear protein (Escherichia coli ampicillin resistance) in S. aureus is an exoprotein in COL strain, predicted to be a superantigen, and speculated to play roles in antibiotic resistance and virulence. The goal of this study was to determine if expression of ear is modulated by single nucleotide polymorphisms in its promoter and coding sequences and whether this gene plays roles in antibiotic resistance and virulence...
December 2017: Journal of Medical Microbiology
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