New futures of sialyated lipo-oligosaccharide structures in campylobacter jejuni
The zoonotic human enteric pathogen Campylobacter jejuni is acquired by humans through contaminated water, poultry, shellfish and pets 1. Motility, chemotaxis, glycosylation and lipo-oligosaccharides (LOS) structures are all different virulence features exploited by C. jejuni to adhere, invade, adapt and survive in a mammalian host 2-11. The most interesting one is the LOS structure, which is phase variable 12, 13. C. jejuni LOS phase variation not only provides host adaptation abilities 14, but also protection against human serum 8. Next, LOS is an important virulence factor used by C. jejuni to invade intestinal epithelial cells 15, 16. To date, five major and distinct LOS biosynthesis gene clusters, here referred to as LOS classes, have been described for C. jejuni 17, and this number is continuously growing 18. Analysis of the LOS biosynthesis gene loci of complete C. jejuni genomes revealed these loci to be highly variable 18, 19. Although the number of C. jejuni LOS classes is continuously growing and its LOS biosynthesis genes found to be highly variable 17, 18, a specific molecule, to be precise, sialic acid, enables us to separate C. jejuni into two main groups. One C. jejuni group that is able to sialylate their LOS structures (LOS class A, B and C) and ones disabled in sialylation of their LOS structures (LOS class D, E and others). Sialic acid transfer to the LOS structures on C. jejuni occurs by two sialyltransferases; a α2,3/α2,8 sialyltransferase named Cst-II 20 and a α2,3 sialyltransferase named Cst-III 19. Interestingly, the two LOS classes A and B, are strongly associated with the post-infectious complications Guillain-Barré Syndrome (GBS) and Miller Fisher Syndrome (GBS and MFS), respectively 21. These two classes harbor the cst-II gene, until now the only functionally established marker for GBS 21, 22. Noteworthy, Cst-II and Cst-III mediated sialylation of LOS structures (LOS classes A, B and C) is also associated with severe gastro-enteritis, bloody stools and another post-infectious complication, Reactive Arthritis 23. A key feature of Cst-II and Cst-III mediated sialylation of LOS structures on C. jejuni is that they mimic similar structures, called gangliosides, on the human peripheral nerves 24. It is thought this molecular mimicry is the most important factor in GBS induction, because in a subset of enteritis patients antibodies are generated that have the ability to cross-react with both C. jejuni ganglioside-like LOS and human nerve gangliosides. Binding of these antibodies will lead to removal of the myelin sheet by macrophages, ensuing loss of nerve function and GBS induction 25. Worth mentioning, approximately 50 - 60% of the C. jejuni enteritis isolates are able to express ganglioside mimics 21, but only 1 in 1000 C. jejuni infections results in the development of GBS 26. Although there are strong indications that cross-reactive antibodies are important for the induction of GBS 27, little is known about the mechanism(s) that lead to the development of these cross-reactive antibodies.
|Promotor||Belkum, A.F. van (Alex) , Neuwenhuis, E.E.S.|
|Publisher||Erasmus MC: University Medical Center Rotterdam|
Louwen, R.P.L.. (2012, March 21). New futures of sialyated lipo-oligosaccharide structures in campylobacter jejuni. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/33081