# Polymicrobial Synergy between Treponema denticola and Porphyromonas gingivalis

> **NIH NIH R00** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $249,000

## Abstract

Project Summary
Polymicrobial communities that exhibit synergistic pathogenicity cause periodontal disease, one of the most
common infections of humans. As a model system for the study of polymicrobial synergy, we are investigating
the interactions of Treponema denticola and Porphyromonas gingivalis. Heterotypic communities develop as
physiologically compatible organisms modulate their own and their partner’s physiology resulting in enhanced
fitness and virulence. Synergistic metabolism can reduce the nutrient requirements of the entire community,
thereby increasing the pathogenic potential. T. denticola and P. ginigvalis display metabolic cross-feeding to
enhance the growth of both bacteria. Additional bacterial members of the subgingival plaque community are
known to cooperate in metabolic exchanges. However, the molecular details of metabolic cross-feeding and how
it functions to drive pathogenicity are understudied. The overall premise of this study is to characterize the
metabolic interactions between T. denticola and P. gingivalis to better understand the pathogenic potential of the
community. Aim 1 will evaluate how glycine is acquired and utilized as a carbon and energy source. Aim 2 will
characterize the response of T. denticola to mutualistic metabolism by enhancing biofilm development and
invasion into gingival epithelial cells. Aim 3 will demonstrate that metabolic cross-feeding enhances the
pathogenicity of T. denticola. Our overall long-term goal is to translate these novel molecular mechanisms into
the development of future therapeutic approaches targeting polymicrobial pathogenic communities. The
candidate, Dr. Miller, has a longstanding interest in the microbiology of periodontal diseases. After completing
the mentored (K99) phase, his goal is to become an assistant professor at a leading research university, where
he plans to continue his research on interbacterial interactions that promote periodontal diseases. This K99/R00
proposal is designed to complement Dr. Miller’s previous research expertise and provide him with the opportunity
to develop the necessary skills and experiences to become an independent research scientist. Dr. Miller will
receive additional training under the guidance of the primary mentor, Dr. Richard Lamont, and co-mentor, Dr.
David Scott. Both mentors were carefully selected for as they each contribute diverse, yet complementary
expertise for the successful completion of this research program. Additionally, Dr. Miller has assembled a
committee of scientists with various backgrounds who will provide oversight and advise his scientific and career
development during his transition to independence.

## Key facts

- **NIH application ID:** 10037674
- **Project number:** 4R00DE028346-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Daniel Patrick Miller
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10037674

## Citation

> US National Institutes of Health, RePORTER application 10037674, Polymicrobial Synergy between Treponema denticola and Porphyromonas gingivalis (4R00DE028346-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10037674. Licensed CC0.

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