# Exploring new virulence factors of the oral spirochete Treponema denticola

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $46,310

## Abstract

Abstract (Parent Grant)
The innate immune system (i.e., complement- and neutrophil-mediated killing) is the first line of defense
against microbial infections. In the oral cavity, the innate immune system is highly active and sustains
the oral microbiota at the stage of symbiosis. As a keystone pathogen, the oral bacterium Treponema
denticola (Td) is highly invasive, establishing itself at the forefront of subgingival plaques where it
directly confronts the host immune response. Td is able to breach host immune defenses, survives, and
even becomes predominant in the pocket when dysbiosis and inflammation worsens (e.g., in severe
and refractory periodontitis). The underlying mechanisms that allow Td to evade the host immune
response remain largely unknown. During the last funding cycle, we have discovered several novel
virulence factors in Td. Among these factors, we found that TDE0362 (a cysteine protease) and
TDE0471 (a sialidase) have unique biochemical and structural features, protect Td from complement
and neutrophils killings, and play pivotal roles in the pathogenicity of Td. We also identified a novel
glycan that modifies Td flagellin proteins and this unique modification is not only essential for the
flagellation and motility of Td but also alters the innate immune response to the flagellins. Building upon
these findings, this renewal aims to elucidate the molecular mechanisms underlying these three novel
pathogenic traits of Td. To achieve this goal, the following three questions will be addressed. (1) What
is the molecular mechanism by which TDE0362 impairs host neutrophil and complement activation? (2)
How does TDE0471 utilize host sialic acids to protect Td from complement killing? (3) How does
glycosylation alter the innate immune response to Td flagellins? Completion of these studies will not
only provide new insights into understanding the pathogenicity of Td at the molecular level, but also
advance our current understanding of the uniqueness and complexity of periodontitis. One of the unique
aspects about keystone pathogens is that while they trigger robust and hostile inflammation, they have
also evolved complex mechanisms to evade host immune defenses, which allow them to thrive in the
pocket, change symbiotic microbiota to dysbiosis, and cause tissue damage. Understanding their
uniqueness and the underlying mechanisms will lead to new strategies to treat and prevent periodontitis.

## Key facts

- **NIH application ID:** 10371498
- **Project number:** 3R01DE023080-09S1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Chunhao Chris Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,310
- **Award type:** 3
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371498

## Citation

> US National Institutes of Health, RePORTER application 10371498, Exploring new virulence factors of the oral spirochete Treponema denticola (3R01DE023080-09S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371498. Licensed CC0.

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