# Characterization of Treponema Denticola-Mediated Interactions With Periodontal Ligament Cells Leading to Persistent Host Cell/Tissue Destruction

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $45,505

## Abstract

Project Summary/Abstract
Periodontal disease is characterized by destruction of the hard and soft tissues that comprise the
periodontium. This destruction translates to a degradation of the extracellular matrices (ECM), which is
mediated by bacterial proteases, host-derived matrix metalloproteinases (MMPs), and other proteases
released by host tissues and immune cells. Furthermore, pathogenic microbes are a catalyst for periodontal
disease pathogenesis since the development of a dysbiosis of the microbiome enhances a persistent immune
response. These bacterial pathogens interact with host tissue and thereby trigger adverse cellular functions,
including a heightened immune response, tissue destruction, and tissue migration. One implicated bacteria, the
oral spirochete, Treponema denticola (T. denticola or Td), is highly associated with periodontal disease (5).
We’ve demonstrated that a Td outer membrane protein complex called dentilisin, contributes to the chronic
activation of pro-MMP-2 in periodontal ligament (PDL) cells (26,27). Dentilisin exposure also triggers increased
expression levels of activators and effectors of active MMP-2 in PDL cells. Despite these advances, there is no
mechanism known for dentilisin-induced MMP-2 activation or PDL cytopathic behaviors leading to disease, or
potential treatment. One possible therapeutic to combat these interactions is nisin. Nisin is a naturally occurring
bacteriocin, widely used food preservative, and probiotic agent naturally made by bacterial species similar to
those in the gut and oral cavity. Our lab demonstrated that nisin is an effective anti-microbial against key
periodontopathic bacteria at low concentrations, including Td, with the potential to disrupt oral biofilm formation
in vitro (11). Importantly, although most nisin related literature documents its role against gram-positive
bacteria, our published work (11) highlights its efficacy against gram-negative bacteria. Furthermore, nisin at
low concentrations is also more effective against certain oral pathogenic versus commensal bacteria; making it
a potentially useful and selective agent for oral applications. Proper clearance of Td may provide a more
symbiotic microbiome and “reset” homeostatic conditions needed for repair, remodeling or regeneration of the
periodontium. Thus, the main hypotheses of this proposal are that T. denticola interactions with PDL
cells mediate adverse effects on homeostasis and cellular functions leading to a compromised cellular
phenotype. Additionally, nisin is a potential therapeutic for abrogating these effects. This hypothesis will
be tested in the following specific aims: 1) Determine the mechanism of dentilisin-induced activation of pro-
MMP-2 in PDL cells; 2) Characterize the effects of T. denticola(Td) challenge on PDL cell processes and
differentiation; 3) Determine whether sub-antimicrobial doses of nisin can abrogate Td/dentilisin-mediated
activation of MMP-2 in PDL cells. Success of this proposal ...

## Key facts

- **NIH application ID:** 10454807
- **Project number:** 5F30DE027598-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Erin Trent Malone
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $45,505
- **Award type:** 5
- **Project period:** 2017-09-05 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454807

## Citation

> US National Institutes of Health, RePORTER application 10454807, Characterization of Treponema Denticola-Mediated Interactions With Periodontal Ligament Cells Leading to Persistent Host Cell/Tissue Destruction (5F30DE027598-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454807. Licensed CC0.

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