A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization
A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization
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DOI：
10.1098/rsob.130202
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发表时间：
2014-01-01
期刊：
影响因子：
5.8
通讯作者：
Ala'Aldeen, Dlawer A. A.
中科院分区：
文献类型：
--
作者：
Mahdavi, Jafar;Pirinccioglu, Necmettin;Ala'Aldeen, Dlawer A. A.
空肠弯曲杆菌是人类食源性胃肠炎的重要原因；由于对宿主和病原体之间复杂的相互作用缺乏了解，因此预防感染的策略受到阻碍。已有研究表明，空肠弯曲菌在体外可与人组织血型抗原结合，而BgAgs在体外可抑制空肠弯曲菌与人肠粘膜的结合。在此，空肠弯曲菌NCTC11168的主要鞭毛亚单位蛋白(FLAA)和主要外膜蛋白(MOMP)被鉴定为BgAg结合粘附素。值得注意的是，MOMP在Thr(268)处是O-糖基化的；以前只有鞭毛蛋白在空肠弯曲菌中是O-糖基化的。MOMP Thr(268)的取代导致与BgAgs的结合显著减少。O-糖链的结构为Gal(β1-3)-GalNAc(β1-4)-GalNAc(β1-4)-GalNAca1-Thr(268)；模拟表明O-糖基化对MOMP的构象有显著影响，从而调节了BgAg的结合能力。MOMP在Thr(268)位的糖基化促进了细胞与细胞的结合、生物膜的形成和与Caco-2细胞的黏附，这是空肠弯曲菌在鸡的最佳定植所必需的，证实了这种O-糖基化在发病机制中的意义。
Campylobacter jejuni is an important cause of human foodborne gastroenteritis; strategies to prevent infection are hampered by a poor understanding of the complex interactions between host and pathogen. Previous work showed that C. jejuni could bind human histo-blood group antigens (BgAgs) in vitro and that BgAgs could inhibit the binding of C. jejuni to human intestinal mucosa ex vivo. Here, the major flagella subunit protein (FlaA) and the major outer membrane protein (MOMP) were identified as BgAg-binding adhesins in C. jejuni NCTC11168. Significantly, the MOMP was shown to be O-glycosylated at Thr(268); previously only flagellin proteins were known to be O-glycosylated in C. jejuni. Substitution of MOMP Thr(268) led to significantly reduced binding to BgAgs. The O-glycan moiety was characterized as Gal(beta 1-3)-GalNAc(beta 1-4)-GalNAc(beta 1-4)-GalNAca1-Thr(268); modelling suggested that O-glycosylation has a notable effect on the conformation of MOMP and this modulates BgAg-binding capacity. Glycosylation of MOMP at Thr(268) promoted cell-to-cell binding, biofilm formation and adhesion to Caco-2 cells, and was required for the optimal colonization of chickens by C. jejuni, confirming the significance of this O-glycosylation in pathogenesis.