# Decoding the glycome of oral Treponema denticola

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $504,324

## Abstract

PROJECT SUMMARY
The bacterium Treponema denticola (Td) is an important and yet understudied oral pathobiont that is highly
associated with periodontitis, necrotic root canals, and endodontic infections. Growing evidence also shows that
Td is implicated in several systemic illnesses such as Alzheimer’s disease and oral squamous cell carcinoma.
As a keystone pathogen, Td shows various pathogenic traits, e.g., cell adherence and invasion, stimulation of
proinflammation, modulation of host immune responses, and inducing osteoclastogenesis (OCG) and alveolar
bone loss. However, bacterial virulence determinants associated with these pathogenic traits remain
largely unknown. For instance, there is a longstanding conundrum as to whether or not Td produces
lipopolysaccharides (LPS), an endotoxin that is of paramount importance to most Gram-negative bacterial
pathogens. Early studies indicate that Td produces LPS; however, later reports from different groups uncover
that Td produces lipooligosaccharide (LOS), lipoteichoic acids or membrane associated lipids. These
inconsistent reports have been a longstanding obstacle to understanding the role of Td in the pathogenesis of
periodontitis and other diseases. During the past five years, we have been striving to address this longstanding
conundrum by using a multidisciplinary approach combining bioinformatics, genetics, glycomics, immunology,
and structural biology along with several cutting-edge techniques and have made significant progress to
understanding the chemical structure, biosynthesis, regulation, and pathogenic role of LPS-like fractions purified
from Td. Based on these preliminary studies, we hypothesize that, instead of LPS/LOS, Td produces a new
class of sulfated glycolipids (SGLs) with a distinct chemical composition and structure, its biosynthesis
is regulated in response to biofilm formation, and that this new type of glycolipids plays a critical role in
the pathophysiology of Td. To test this hypothesis, the following three aims are proposed: (1) Delineating the
chemical composition, glycosidic linkage, and key genetic determinants required for the biosynthesis of SGLs;
(2) Elucidating the regulatory mechanism of SGLs and their role in Td cell structure, motility, and biofilm
formation; and (3) Investigating the role of SGLs in Td-induced OCS and alveolar bone loss. To the best of our
knowledge, this is the first project to mechanistically investigate the chemical composition, glycosidic linkages,
biosynthesis, regulation, and roles of SGLs in the pathophysiology of Td. Completion of this project will provide
new insights into understanding the glycome of Td and its role in the pathogenesis of oral infections and systemic
diseases. In addition, this application will open new avenues to investigate SGLs in other oral pathogens.

## Key facts

- **NIH application ID:** 10945928
- **Project number:** 1R01DE034063-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Chunhao Chris Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $504,324
- **Award type:** 1
- **Project period:** 2024-08-12 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945928

## Citation

> US National Institutes of Health, RePORTER application 10945928, Decoding the glycome of oral Treponema denticola (1R01DE034063-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10945928. Licensed CC0.

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