当前位置: X-MOL 学术AMB Express › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Oral administration of recombinant Bacillus subtilis spores expressing mutant staphylococcal enterotoxin B provides potent protection against lethal enterotoxin challenge
AMB Express ( IF 3.5 ) Pub Date : 2020-12-14 , DOI: 10.1186/s13568-020-01152-x
Zhile Xiong , Jialiang Mai , Fei Li , Bingshao Liang , Shuwen Yao , Zhuwei Liang , Chao Zhang , Fei Gao , Xiaolan Ai , Jielin Wang , Yan Long , Min Yang , Sitang Gong , Zhenwen Zhou

Pathogenicity of Staphylococcus aureus is induced by staphylococcal enterotoxin B (SEB). A mutant form of SEB (mSEB) is immunogenic as well as less toxic. Recombinant mSEB and SEB were expressed in pET28a prokaryotic plasmids. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in mSEB-stimulated macrophages were lower than those in SEB-stimulated macrophages (p < 0.001, p < 0.01 respectively). Using CotC as a fusion protein, we constructed recombinant Bacillus subtilis spores expressing mSEB on the spore surface and evaluated their safety and protective efficacy via mouse models. Oral administration of mSEB-expressing spores increased SEB-specific IgA in feces and SEB-specific IgG1 and IgG2a in the sera, compared with mice in naïve and CotC spore-treated groups (p < 0.001, p < 0.01, p < 0.001 respectively). Six weeks following oral dosing of recombinant spores, significant differences were not found in the serum biochemical indices between the mSEB group and the naïve and CotC groups. Furthermore, oral administration of mSEB spores increased the survival rate by 33.3% in mice intraperitoneally injected with 5 µg of wild-type SEB plus 25 µg lipopolysaccharide (LPS). In summation, recombinant spores stably expressing mSEB were developed, and oral administration of such recombinant spores induced a humoral immune response and provided protection against SEB challenge in mice.



中文翻译:

口服施用表达突变葡萄球菌肠毒素B的重组枯草芽孢杆菌孢子可有效抵抗致命的肠毒素攻击

金黄色葡萄球菌的致病性是由葡萄球菌肠毒素B(SEB)诱导的。SEB的突变形式(mSEB)具有免疫原性,并且毒性较低。重组mSEB和SEB在pET28a原核质粒中表达。mSEB刺激的巨噬细胞的肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)水平低于SEB刺激的巨噬细胞( 分别为p  <0.001,p <0.01)。使用CotC作为融合蛋白,我们构建了重组枯草芽孢杆菌孢子在孢子表面表达mSEB,并通过小鼠模型评估其安全性和保护功效。与单纯和经CotC孢子处理的小鼠相比,口服表达mSEB的孢子可增加粪便中SEB特异性IgA以及血清中SEB特异性IgG1和IgG2a(p  <0.001,p  <0.01,p 分别<0.001)。口服口服重组孢子六周后,mSEB组与未处理组和CotC组之间的血清生化指标没有发现显着差异。此外,在腹膜内注射5 µg野生型SEB加25 µg脂多糖(LPS)的小鼠中,口服mSEB孢子可使存活率提高33.3%。总之,开发了稳定表达mSEB的重组孢子,并且这种重组孢子的口服给药诱导了体液免疫应答并在小鼠中提供了针对SEB攻击的保护。

更新日期:2020-12-14
down
wechat
bug