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 99 (Supplement_3) ◽  
pp. 205-206
Author(s):  
Jia-yi Zhou ◽  
Zhen-hua Liu ◽  
Chunqi Gao ◽  
Huichao Yan ◽  
Xiu-qi Wang

Abstract Enterotoxigenic E. coli causes severe infectious diarrhea with high morbidity and mortality in weanling pigs mainly through the production of heat-stable enterotoxins. Iturin A, originally isolated from the insect Hyalophora cecropia, exerts strong antibiotic activity against Gram-positive and Gram-negative bacteria. Thus, our study investigated whether iturin A could protect the intestinal epithelium from the insults of E. coli Rosetta containing the gene coding for heat-stable enterotoxin b (STb-Rosetta). Twenty-eight piglets were divided into four groups and were orally administered PBS (control), 0.16 g/kg BW iturin A, 2 × 109 CFU STb-Rosetta, and 0.16 g/kg BW iturin A + 2 × 109 CFU STb-Rosetta respectively for 8 days. The intestinal epithelial morphology and barrier function were assessed by H&E staining and Ussing chamber, and the growth advantage in enteroids derived from jejunal crypts of piglets in each group was used to evaluate the intestinal stem cell (ISC) activity. The results showed that iturin A increased the average daily gain (ADG) and average daily feed intake (ADFI) of piglets exposed to STb-Rosetta (P < 0.05). Meanwhile, STb-Rosetta-induced decrease in jejunum weight and damage to jejunal morphology and barrier function were significantly improved after iturin A supplementation (P < 0.05). Furthermore, the jejunal crypt cells from piglets in the iturin A + STb-Rosetta group had greater growth advantages of ISCs compared with the STb-Rosetta group, including enteroid forming efficiency, surface area, budding efficiency, and branching coefficient (P < 0.05). Our results indicate that iturin A protects against STb-Rosetta-induced intestinal mucosal injury, which provides an intervention strategy that regulates the function of ISCs in the high turnover-rate crypt-villous axis under ETEC infection. This study was supported by the National Natural Science Foundation of China (31872389, 32072777) and Basic and Applied Basic Research Foundation of Guangdong Province (2019B1515210021).


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.


Gene Reports ◽  
2021 ◽  
Vol 23 ◽  
pp. 101099
Author(s):  
Amir Namvar Vansofla ◽  
Shahram Nazarian ◽  
Emad Kordbache ◽  
Javad Fathi

EBioMedicine ◽  
2021 ◽  
Vol 67 ◽  
pp. 103353
Author(s):  
Jiawu Wan ◽  
Ting Wang ◽  
Jing Xu ◽  
Tao Ouyang ◽  
Qianruo Wang ◽  
...  

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

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammed Yahya Ahmed ◽  
Hashim Abdalbagi Ali ◽  
Babbiker Mohammed Taher Gorish ◽  
Sara Omer Ali ◽  
Eman Saif Aldein Abdalrhim ◽  
...  

Staphylococcal food poisoning is an intoxication that results from the consumption of improperly prepared or stored foods containing sufficient amounts of one or more preformed S. aureus enterotoxins. Nowadays, many researchers worldwide noted an emergence of resistant strains such as Staphylococci particularly for the antibiotic methicillin. Therefore, this study was aimed to determine the existence of Staphylococcus aureus and its enterotoxins, mecA genes, in selected food samples. A total of 400 selected food samples were collected from different areas in Khartoum State. The selected foods included cheese, meat products, fish, and raw milk. One hundred samples from each type of food were cultivated, and the resultant growth yielded 137 (34.25%) S. aureus, 126 (31.5%) bacteria other than S. aureus, and 137 (34.25%) yielded no growth. Eighty-four of the 137 S. aureus isolates were randomly selected and tested for the presence of mecA and enterotoxin genes. The oxacillin sensitivity test showed that 15 (11%) of 137 S. aureus isolates were oxacillin resistant. The PCR assay showed that the mecA gene was detected in 15 of 84 (17%) S. aureus isolates. Simultaneously, only 2 (2.385%) out of 84 S. aureus isolates showed an enterotoxin B gene product. There was a relatively moderate prevalence of methicillin-resistant Staphylococcus aureus with very low frequency of enterotoxin B gene in different kinds of selected food samples collected from Khartoum State. These findings elucidate the increased risk on public in Khartoum being affected by Staphylococcal food poisoning upon consumption of dairy or meat products prepared in unhygienic conditions that could lead to intoxication by Staphylococcus aureus enterotoxins.


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