# Impact of ß-glucan metabolism on the development of pathogenic biofilms

> **NIH NIH R03** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $159,500

## Abstract

Project Summary/Abstract
 Periodontitis is a bacterially induced chronic inflammation of the tooth supporting tissues
that may result in alveolar bone destruction and tooth loss. Tannerella forsythia (Tf), a member
of the ‘red-complex’ bacteria group, is one of the major pathogens implicated in periodontitis. T.
forsythia has been shown to co-aggregate with the ‘bridge-bacterium’ Fusobacterium nucleatum
(Fn) to form synergistic co-biofilms in vitro and induce alveolar bone loss in mice when co-
infected with Fn. The overall goal of this proposal is to determine the molecular mechanisms of
T. forsythia -F. nucleatum intergeneric interactions to better understand the pathogenesis of
periodontitis. Our preliminary data show that a Tf secreted ß-glucanase enzyme (GlcA) whose
expression is induced in response to Fn sensing plays a significant role in the development of mixed
biofilms. We showed that this enzyme hydrolyzes ß-glucans into glucose, which serves as a nutrient for Fn
to promote its biomass in Tf -Fn co-biofilms. Our data showed that the increased glucose availability did not
affect Tf biomass but it rather enhanced the production of methylglyoxal (MGO), a highly reactive dicabonyl
compound toxic to bacterial and host cells.
 The goal of this proposal is to understand the mechanistic basis of Tf-Fn interactions
and how metabolic interactions between these two species contribute to the
development of the dental plaque, dysbiosis and inflammation. Our working hypothesis is that
b-glucanase produced by Tf in response to Fn, and possible other stimuli, releases glucose from dietary b-
glucans as a nutrient for the microbial community at large and as a metabolic precursor for MGO secretion
to favor microbial dysbiosis. To interrogate this hypothesis, we propose two specific aims: Aim 1:
To define the molecular mechanism of regulation of Tf GlcA operon in response to Fn sensing.
We will analyze the mechanism and function of ECF sigma-anti sigma system that is predicted
to drive Tf glcA ß-glucanase operon to respond stimulate with Fn and other stimuli, and; Aim 2
To determine the mechanisms by which Fn resists Tf-produced methylglyoxal and how
hydrolyzed glucans impact microbial community structure. Here, we will determine the molecular
mechanisms by which Fn detoxifies MGO produced by Tf in biofilms and promote dental plaque
development.
 Successful completion of this study will form the foundation for future investigations exploring
the unique ability of Tf glucanase-MGO axis in promoting microbial dysbiosis and subsequently develop
glucanase targeting inhibitors to block the synergistic Tf-Fn associations and dental plaque
development for the treatment of periodontitis.

## Key facts

- **NIH application ID:** 10187549
- **Project number:** 5R03DE028928-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Kiyonobu Homma
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $159,500
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187549

## Citation

> US National Institutes of Health, RePORTER application 10187549, Impact of ß-glucan metabolism on the development of pathogenic biofilms (5R03DE028928-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10187549. Licensed CC0.

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