# P. gingivalis interactions with gingival epithelial cells

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2022 · $367,971

## Abstract

The epithelial layer of host mucosal surfaces presents an initial interface for colonizing microorganisms. In
addition to constituting a physical barrier to the ingress of organisms, epithelial cells can sense and respond to
the presence of bacteria through an elaborate signaling network that can also communicate information to the
underlying immune effector cells in the mucosa. Bacteria that colonize the epithelial surface often engage
epithelial cells in a complex molecular dialog which results in significant changes to the host cell transcriptional
program and can fundamentally alter epithelial properties. Moreover, in vivo, bacteria on epithelial surfaces tend
to accumulate into polymicrobial communities, and communities of organisms can exhibit properties distinct from
individual constituent species in isolation. Ultimately, it is the collective action of the community organisms that
determines the impact of the microbial challenge on the host.
Our ongoing studies of gingival epithelial cells (GECs) show that the periodontal pathogen Porphyromonas
gingivalis can regulate the activity of a number of transcription factors and co-factors which control inflammation,
cell viability and proliferation. These include β-catenin which is proteolytically activated by P. gingivalis, and
FOXO1 which is activated by site specific dephosphorylation. Activation of β-catenin and FOXO1 by P. gingivalis
leads to the regulation of ZEB2, a transcription factor pivotal for governing essential epithelial properties and
tissue integrity. Moreover ZEB2 can control the maturation of immune cells and the production of inflammatory
mediators such as IL-6. We also found that manipulation of the β-catenin-FOXO1 axis by P. gingivalis can be
antagonized by Streptococcus gordonii and S. oralis, but remains unaffected by other common oral streptococci.
Hence our hypotheses are that i) the interplay between β-catenin and FOXO1 controls ZEB2 expression in
response to P. gingivalis, and impacts epithelial cell characteristics with relevance to the maintenance of tissue
homeostasis; and ii) specific oral community profiles can modulate the influence of P. gingivalis on epithelial
signaling pathways that regulate β-catenin and FOXO1 function. The Aims of the project are thus: 1. To
characterize the functional integration of β-catenin and FOXO1 in the control of ZEB2 by P. gingivalis. 2. To
determine the functional relevance of site-specific dephosphorylation of FOXO1 by P. gingivalis for the FOXO1
transcriptional program and ZEB2 regulation. 3. To characterize the mechanisms by which S. gordonii can
subvert P. gingivalis-induced activation of the β-catenin-FOXO1-ZEB2 axis. Successful completion of this
project will define novel mechanisms for the integration and control of epithelial cell transcription factors, and
characterize modulation of these pathways by P. gingivalis both as a single species infection and in the context
of a community. These studies will increase our unders...

## Key facts

- **NIH application ID:** 10400103
- **Project number:** 5R01DE011111-29
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Richard J Lamont
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,971
- **Award type:** 5
- **Project period:** 1995-04-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400103

## Citation

> US National Institutes of Health, RePORTER application 10400103, P. gingivalis interactions with gingival epithelial cells (5R01DE011111-29). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10400103. Licensed CC0.

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