Exploiting the Campylobacter jejuni protein glycosylation system for glycoengineering vaccines and diagnostic tools directed against brucellosis.
Exploiting the Campylobacter jejuni protein glycosylation system for glycoengineering vaccines and diagnostic tools directed against brucellosis.
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DOI：
10.1186/1475-2859-11-13
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发表时间：
2012-01-25
影响因子：
6.4
通讯作者：
Feldman MF
中科院分区：
文献类型：
--
作者：
Iwashkiw JA;Fentabil MA;Faridmoayer A;Mills DC;Peppler M;Czibener C;Ciocchini AE;Comerci DJ;Ugalde JE;Feldman MF
针对与蛋白质缀合的表面多糖的免疫应答在预防细菌病原体的定殖和感染中是有效的。目前，这些缀合物疫苗的生产需要复杂的合成化学来获得、活化多糖并将多糖连接到蛋白质载体上。通过工程化细菌糖基化机器产生的糖蛋白已被提出是传统缀合方法的可行替代方案。在这项工作中，我们表达了C。空肠寡糖基转移酶（OTase）PglB，负责小肠结肠炎耶尔森氏菌O 9细胞中的N-连接蛋白糖基化以及合适的受体蛋白（AcrA）。受体蛋白质的MS分析表明，在体内转移的N-甲酰perosamine的聚合物的AcrA。因为Y.由于小肠结肠炎菌O 9和流产布鲁氏菌具有相同的O多糖结构，我们探索了所得糖蛋白在布鲁氏菌病疫苗学和诊断中的应用，布鲁氏菌病是最常见的人畜共患病之一，每年有超过50万新病例。将糖蛋白注射到小鼠体内产生了识别布鲁氏菌O抗原的IgG应答，尽管这种应答对强毒B的攻击没有保护作用。流产菌株包被在磁珠上的重组糖蛋白可有效区分未感染和感染的牛血清。细菌工程糖蛋白在未来一系列诊断和免疫保护机会的开发中显示出广阔的应用前景。
Immune responses directed towards surface polysaccharides conjugated to proteins are effective in preventing colonization and infection of bacterial pathogens. Presently, the production of these conjugate vaccines requires intricate synthetic chemistry for obtaining, activating, and attaching the polysaccharides to protein carriers. Glycoproteins generated by engineering bacterial glycosylation machineries have been proposed to be a viable alternative to traditional conjugation methods. In this work we expressed the C. jejuni oligosaccharyltansferase (OTase) PglB, responsible for N-linked protein glycosylation together with a suitable acceptor protein (AcrA) in Yersinia enterocolitica O9 cells. MS analysis of the acceptor protein demonstrated the transfer of a polymer of N-formylperosamine to AcrA in vivo. Because Y. enterocolitica O9 and Brucella abortus share an identical O polysaccharide structure, we explored the application of the resulting glycoprotein in vaccinology and diagnostics of brucellosis, one of the most common zoonotic diseases with over half a million new cases annually. Injection of the glycoprotein into mice generated an IgG response that recognized the O antigen of Brucella, although this response was not protective against a challenge with a virulent B. abortus strain. The recombinant glycoprotein coated onto magnetic beads was efficient in differentiating between naïve and infected bovine sera. Bacterial engineered glycoproteins show promising applications for the development on an array of diagnostics and immunoprotective opportunities in the future.
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DOI：
10.1016/j.ijantimicag.2010.06.013
发表时间：
2010-11-01
影响因子：
10.8
作者：
Pappas, Georgios
通讯作者：
Pappas, Georgios
影响因子：
3.2
作者：
Kelly, J;Jarrell, H;Szymanski, CM
通讯作者：
Szymanski, CM
影响因子：
6.2
作者：
Fugier, Emilie;Pappas, Georgios;Gorvel, Jean-Pierre
通讯作者：
Gorvel, Jean-Pierre
DOI：
10.1073/pnas.0500044102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Feldman, MF;Wacker, M;Aebi, M
通讯作者：
Aebi, M
影响因子：
2.1
作者：
Qu, Hong;Xin, Yi;Ma, Yufang
通讯作者：
Ma, Yufang