Because polysaccharides represent the predominant structures on the bacterial cell surface, they are important in the interaction between the pathogen, host, and environment. To summarize the reports described in Subheadings 2.-4., C. jejuni carbohydrates are involved in many cellular functions, including assembly of the flagellar filament (73), which we now realize is a type III-like secretory apparatus necessary for the release of invasion/colonization proteins (14,15), motility (73), assembly of the TFSS that affects DNA uptake and natural transformation (79), adherence and invasion in vitro (41,54,76), colonization, and disease in vivo (41,64,68,76-78), molecular mimicry of gangliosides (82), autoimmunity leading to GBS (48), maintenance of cell surface charge (41), serum resistance (41,53), antigenic (53,60,83) and phase variation (41,54,57,83,84). Considering the importance of glycoconjugates in C. jejuni biology and based on the hypothesis that glycoconjugates have evolved in bacteria to enable them to become established in their preferred environmental niches, it is not surprising that these sugars play critical roles in C. jejuni survival and persistence.
Further characterization of the conserved campylobacter ^-linked glycosylation pathway may lead to the development of novel therapeutic agents directed against the common bacterial heptasaccharide, or against enzymes involved in its biosynthesis. Because inactivation of the pathway also inhibits colonization, we may identify potential
Fig. 9. (Continued) T68-73. The fragment ions originating from the sequential loss of the oligosaccharide residues are indicated in the spectrum, as are the peptide fragment ions. The oligosaccharide is linked to the peptide via the unusual 288.1 Da glycan that was later identified as bacillos-amine (Bac). (C) Second-generation MS/MS analysis of the glycopeptide fragment ion at m/z 937.4. The observation of the b3+288.1 fragment ion at m/z 605.3 clearly indicated that the oligosaccharide is ^-linked to Asn70.
targets for disease intervention, or crucial processes necessary for host-pathogen interactions. Studies may also identify unique glycosyltransferases (such as PglB) with potential commercial applications, including the enormous potential for glycoengineering. Further studies using campylobacter as the model system will aid in understanding the importance of protein glycosylation, and the pathways involved for biosynthesis that will have applications in both bacterial and eukaryotic glycobiology and infectious diseases.
Although there is more variability in the flagellin O-linked glycans, this pathway is also an attractive therapeutic target for two obvious reasons: (1) Pse is common to two other important human pathogens (H. pylori and P. aeruginosa) and (2) inhibition of Pse biosynthesis results in inhibition of flagellar assembly and motililty in both campylobacter and helicobacter. In addition, further elucidation of the biosynthetic pathway will identify novel enzymes involved in Pse biosynthesis. Indeed, enzymes identified from all four pathways: N- and O-linked protein glycosylation, LOS, and CPS may be useful in industrial applications including glycoengineering. For example, there is an interest to produce synthetic gangliosides using C. jejuni enzymes for use in cancer therapy (85). Further study of these pathways can also lead to novel strategies for the detection and identification of these pathogens.
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