staphylococcal enterotoxin b
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2021 ◽  
Vol 12 ◽  
Author(s):  
Ganggang Bai ◽  
Yanhong Ge ◽  
Yuhong Su ◽  
Shuo Chen ◽  
Xingcheng Zeng ◽  
...  

Staphylococcal enterotoxin B (SEB) simultaneously crosslinks MHC class II antigen and TCR, promoting proliferation of T cells and releasing a large number of toxic cytokines. In this report, we computationally examined the possibility of using a single-chain biparatopic bispecific antibody to target SEB and prevent TCR binding. The design was inspired by the observation that mixing two anti-SEB antibodies 14G8 and 6D3 can block SEB-TCR activation, and we used 14G8-6D3-SEB tertiary crystal structure as a template. Twelve simulation systems were constructed to systematically examine the effects of the designed bispecific scFV MB102a, including isolated SEB, MB102a with different linkers, MB102a-SEB complex, MB102a-SEB-TCRβ complex, MB102a-SEB-TCR-MHC II complex, and MB102a-SEB-MHC II. Our all atom molecular dynamics simulations (total 18,900 ns) confirmed that the designed single-chain bispecific antibody may allosterically prevent SEB-TCRβ chain binding and inhibit SEB-TCR-MHC II formation. Subsequent analysis indicated that the binding of scFV to SEB correlates with SEB-TCR binding site motion and weakens SEB-TCR interactions.


2021 ◽  
Vol 12 ◽  
Author(s):  
Martina Kunkl ◽  
Carola Amormino ◽  
Silvana Caristi ◽  
Valentina Tedeschi ◽  
Maria Teresa Fiorillo ◽  
...  

The inflammatory activity of staphylococcal enterotoxin B (SEB) relies on its capacity to trigger polyclonal T-cell activation by binding both T-cell receptor (TCR) and costimulatory receptor CD28 on T cells and MHC class II and B7 molecules on antigen presenting cells (APC). Previous studies highlighted that SEB may bind TCR and CD28 molecules independently of MHC class II, yet the relative contribution of these interactions to the pro-inflammatory function of SEB remained unclear. Here, we show that binding to MHC class II is dispensable for the inflammatory activity of SEB, whereas binding to TCR, CD28 and B7 molecules is pivotal, in both human primary T cells and Jurkat T cell lines. In particular, our finding is that binding of SEB to B7 molecules suffices to trigger both TCR- and CD28-mediated inflammatory signalling. We also provide evidence that, by strengthening the interaction between CD28 and B7, SEB favours the recruitment of the TCR into the immunological synapse, thus inducing lethal inflammatory signalling.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 617
Author(s):  
Young-Seob Lee ◽  
Kwan-Woo Kim ◽  
Dahye Yoon ◽  
Geum-Soog Kim ◽  
Dong-Yeul Kwon ◽  
...  

Korean ginseng has been widely used in Eastern medicine for thousands of years. The contents of the compounds in ginseng roots change depending on the amount of steaming and drying, and the drying method used. Black ginseng (BG) is the Korean ginseng processed by repeated steaming and drying. In this study, 5-year-old fresh Korean ginseng roots were steamed and dried 3 or 5 times, and we investigated how many cycles of steaming and drying are preferable for antivirulence activities against methicillin-resistant Staphylococcus aureus (MRSA). As a result, the antivirulence activities was increased by the treatment of BG that was steamed and dried three times, and the effect was further increased by five-time processed BG. Moreover, an ELISA showed that the TNF-α production of RAW264.7 cells stimulated by MRSA supernatants was inhibited by subinhibitory concentrations of BG extract. The expression of Hla, staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB), an important virulence factor in the pathogenicity of MRSA, was found to decrease when bacterial cells were treated with BG extract. The antivirulence activities of BG were not simply due to pathogen growth inhibition; the BG extract was shown to decrease agrA, hla, sea, and seb expression in MRSA. Therefore, BG strongly reduces the secretion of the virulence factors produced by Staphylococcus aureus, suggesting that a BG-based structure may be used for the development of drugs aimed at staphylococcal virulence-related exoproteins. This study suggests that BG could be used as a promising natural compound in the food and pharmaceutical industry.


Structure ◽  
2021 ◽  
Author(s):  
Mary Hongying Cheng ◽  
Rebecca A. Porritt ◽  
Magali Noval Rivas ◽  
James M. Krieger ◽  
Asli Beyza Ozdemir ◽  
...  

Nanoscale ◽  
2021 ◽  
Author(s):  
Li Li Tian ◽  
Chun Hong Li ◽  
Qi Chao Ye ◽  
Yuan Fang Li ◽  
Cheng Zhi Huang ◽  
...  

Staphylococcal enterotoxin B (SEB) is a typical biological toxin that causes food poisoning. Currently reported SEB detection methods had the drawbacks of sophisticated sample preparation, time-consuming and labor-intensive. Herein, we...


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