# Exploring new virulence factors of the oral spirochete Treponema denticola

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $392,565

## Abstract

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 motile and 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 periodontal 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 found
that 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 specific 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? Addressing these questions 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 the 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
oral cavity, change symbiotic microbiota to dysbiosis, and cause tissue damage. In this regard,
understanding their uniqueness and underlying mechanisms will lead to new strategies to treat and
prevent periodontitis.

## Key facts

- **NIH application ID:** 10369723
- **Project number:** 5R01DE023080-10
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Chunhao Chris Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,565
- **Award type:** 5
- **Project period:** 2013-07-17 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369723

## Citation

> US National Institutes of Health, RePORTER application 10369723, Exploring new virulence factors of the oral spirochete Treponema denticola (5R01DE023080-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10369723. Licensed CC0.

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