Role of sialidase in glycoprotein utilization by Tannerella forsythia

Abstract

The major bacterial pathogens associated with periodontitis includeTannerella forsythia. We previously discovered that sialic acid stimulates biofilm growth ofT. forsythia, and that sialidase activity is key to utilization of sialoconjugate sugars and is involved in host–pathogen interactionsin vitro. The aim of this work was to assess the influence of the NanH sialidase on initial biofilm adhesion and growth in experiments where the only source of sialic acid was sialoglycoproteins or human oral secretions. After showing thatT. forsythiacan utilize sialoglycoproteins for biofilm growth, we showed that growth and initial adhesion with sialylated mucin and fetuin were inhibited two- to threefold by the sialidase inhibitor oseltamivir. A similar reduction (three- to fourfold) was observed with ananHmutant compared with the wild-type. Importantly, these data were replicated using clinically relevant serum and saliva samples as substrates. In addition, the ability of thenanHmutant to form biofilms on glycoprotein-coated surfaces could be restored by the addition of purified NanH, which we show is able to cleave sialic acid from the model glycoprotein fetuin and, much less efficiently, 9-O-acetylated bovine submaxillary mucin. These data show for the first time that glycoprotein-associated sialic acid is likely to be a keyin vivonutrient source forT. forsythiawhen growing in a biofilm, and suggest that sialidase inhibitors might be useful adjuncts in periodontal therapy.