Role of sialidase in glycoprotein utilization by Tannerella forsythia

Abstract

The major bacterial pathogens associated with periodontitis include Tannerella forsythia. We previously discovered that sialic acid stimulates biofilm growth of T. forsythia, and that sialidase activity is key to utilization of sialoconjugate sugars and is involved in host–pathogen interactions in 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 that T. forsythia can 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 a nanH mutant compared with the wild-type. Importantly, these data were replicated using clinically relevant serum and saliva samples as substrates. In addition, the ability of the nanH mutant 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 key in vivo nutrient source for T. forsythia when growing in a biofilm, and suggest that sialidase inhibitors might be useful adjuncts in periodontal therapy.

Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection

“…Interestingly, recent evidence has also indicated that neuraminidase activity may impact biofilm formation. Indeed, reductions in biofilm biomass in vitro have been observed in neuraminidase-deficient and neuraminidase inhibitor-treated S. pneumoniae as well as in Pseudomonas aeruginosa and Tannerella forsythia (30)(31)(32)(33). These findings are generally supported by animal models, where NanA-deficient pneumococci are impaired in their ability to cause nasal colonization, otitis media, pneumonia, and bacteremia (24,34).…”

Aeromonas salmonicida Growth in Response to Atlantic Salmon Mucins Differs between Epithelial Sites, Is Governed by Sialylated and N -Acetylhexosamine-Containing O -Glycans, and Is Affected by Ca 2+

“…The effect of mucins on A. salmonicida growth was analyzed in defined medium (DM) with and without the addition of 2 g/liter glucose (DMϩ versus DM-), since A. salmonicida may be able to utilize mucins as a carbon source, similarly to some other microbes (28)(29)(30)(31). We verified that alamarBlue (a redox indicator that yields a signal in response to metabolic activity), used to analyze the growth of A. salmonicida, closely followed the growth curves (measured in CFU per milliliter) and thus is an accurate measure of A. salmonicida growth within the ranges of growth and bacterial density at which we performed all experiments presented in this study (r 2 ϭ 0.99) (Fig.…”

Estimation of Levels of Salivary Mucin, Amylase and Total Protein in Gingivitis and Chronic Periodontitis Patients

“…sialomucins) acts as key in vivo nutrient source for tannerella forsythia (due to its sialidase activity), a key pathogen in chronic periodontitis, when growing in a biofilm [32]. This suggests that various mucinase inhibitors might also be useful as a part of host modulation therapy in the treatment of periodontitis.…”