INVESTIGATING THE NON-2-ULOSONIC ACID BIOSYNTHESIS PATHWAY WITHIN THE S-LAYER GLYCOSYLATION LOCUS OF TANNERELLA FORSYTHIA

Tannerella forsythia is an anaerobic, Gram-negative pathogen which was originally isolated from the human oral cavity of periodontal disease patients. As a member of the “red complex” bacteria, it is implicated in the pathogenesis of severe and chronic periodontitis. Its two-dimensional crystalline surface layer (S-layer) is composed of two glycoproteins and has been shown to play a key role in adhesion, invasion and modulation of pro-inflammatory cytokine expression, possibly through Th17 suppression¹. Our group’s elucidation of the S-layer glycan structure identified the presence of a terminal modified non-2-ulosonic acid (NulO)². While initial studies were in better accordance with a pseudaminic acid (Pse5Am7Gc) terminal sugar, a bioinformatic analysis of the T. forsythia genome based on the NulO biosynthesis pathways of Campylobacter and Helicobacter spp. points towards the presence of legionaminic acid. To shed light on the identity of this sugar residue, we have started investigating a cluster of candidate biosynthetic genes (i.e. TF2075, TF2074, TF2065, and TF2059).

Here, we present our findings from the functional characterization of these putative sugar-biosynthetic enzymes. In conjunction with future experiments, our findings may not only provide access to a rare sugar that may be used for vaccine design, but also contribute to understanding its role in pathogenesis, its impact on the physiology of T. forsythia, and its influence on the organism’s lifestyle. This will eventually pinpoint novel targets for the treatment of periodontal disease.

The work was supported by the Austria Science Fund and was assisted through the use of NRC facilities.