structural heterogeneity of terminal glycans in campylobacter jejuni lipooligosaccharides结构的异质性在空肠弯曲杆菌lipooligosaccharides终端聚糖.pdf

Structural Heterogeneity of Terminal Glycans in Campylobacter jejuni Lipooligosaccharides Evgeny A. Semchenko, Christopher J. Day, Marc Moutin, Jennifer C. Wilson, Joe Tiralongo, Victoria Korolik* Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia Abstract Lipooligosaccharides of the gastrointestinal pathogen Campylobacter jejuni are regarded as a major virulence factor and are implicated in the production of cross-reactive antibodies against host gangliosides, which leads to the development of ´ autoimmune neuropathies such as Guillain-Barre and Fisher Syndromes. C. jejuni strains are known to produce diverse LOS structures encoded by more than 19 types of LOS biosynthesis clusters. This study demonstrates that the final C. jejuni LOS structure cannot always be predicted from the genetic composition of the LOS biosynthesis cluster, as determined by novel lectin array analysis of the terminal LOS glycans. The differences were shown to be partially facilitated by the differential on/ off status of three genes wlaN, cst and cj1144-45. The on/off status of these genes was also analysed in C. jejuni strains grown in vitro and in vivo, isolated directly from the host animal without passaging, using immunoseparation. Importantly, C. jejuni strains 331, 421 and 520 encoding cluster type C were shown to produce different LOS, mimicking asialo GM1, asialo GM2 and a heterogeneous mix of gangliosides and other glycoconjugates respectively. In addition, individual C. jejuni colonies were shown to consistently produce heterogeneous LOS structures, irrespective of the cluster type and the status of phase variable genes. Furthermore we describe C. jejuni strains (351 and 375) with LOS clusters that do not match any of the previously described LOS c