Identifying the targets and functions ofN-linked protein glycosylation inCampylobacter jejuni

Campylobacter jejuniis a major cause of bacterial gastroenteritis in humans that is primarily associated with the consumption of inadequately prepared poultry products, since the organism is generally thought to be asymptomatic in avian species. Unlike many other microorganisms,C. jejuniis capable of performing extensive post-translational modification (PTM) of proteins byN- andO-linked glycosylation, both of which are required for optimal chicken colonization and human virulence. The biosynthesis and attachment ofN-glycans toC. jejuniproteins is encoded by thepgl(protein glycosylation) locus, with the PglB oligosaccharyltransferase (OST) enablingen bloctransfer of a heptasaccharideN-glycan from a lipid carrier in the inner membrane to proteins exposed within the periplasm. Seventy-eightC. jejuniglycoproteins (represented by 134 sites of experimentally verifiedN-glycosylation) have now been identified, and include inner and outer membrane proteins, periplasmic proteins and lipoproteins, which are generally of poorly defined or unknown function. Despite our extensive knowledge of the targets of this apparently widespread process, we still do not fully understand the roleN-glycosylation plays biologically, although several phenotypes, including wild-type stress resistance, biofilm formation, motility and chemotaxis have been related to a functionalpglsystem. Recent work has described enzymatic processes (nitrate reductase NapAB) and antibiotic efflux (CmeABC) as major targets requiringN-glycan attachment for optimal function, and experimental evidence also points to roles in cell bindingviaglycan-glycan interactions, protein complex formation and protein stability by conferring protection against host and bacterial proteolytic activity. Here we examine the biochemistry of theN-linked glycosylation system, define its currently known protein targets and discuss evidence for the structural and functional roles of this PTM in individual proteins and globally inC. jejunipathogenesis.