# Molecular Aspects of Oral Plaque Formation

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $365,750

## Abstract

Polymicrobial infections are inherently more complex than mono-species infections, and this complexity has
been a significant barrier to both a fuller appreciation of pathogenic mechanisms, and to the development of
effective measures to control or prevent the disease. Periodontal diseases typify polymicrobial diseases, and
are among the most common infections of humans. Although certain organisms, such as Porphyromonas
gingivalis, are considered key pathogens, it is the polymicrobial community as a whole that initiates and drives
the disease. While interspecies interactions within communities shape overall pathogenic potential, study of
virulence mechanisms has been largely restricted to individual organisms in monoculture. In this proposal we
will molecularly dissect the mechanistic basis of polymicrobial interactions in a model community of P. gingivalis
with the antecedent colonizer S. gordonii. Our preliminary data have established multimodal interactions
between P. gingivalis and S. gordonii. Detection of the streptococcal metabolite 4 aminobenzoate (pABA) by P.
gingivalis, or interactions between the Mfa1 fimbriae and the streptococcal SspA/B surface protein, incite
disparate signaling events that are transduced through a tyrosine kinase/phosphatase signal integration hub. In
vivo colonization is enhanced by pABA-dependent signaling, but virulence in a murine bone loss model is
diminished. In contrast, interspecies coadhesion increases pathogenic potential in this model. Our data further
suggest that that the synergistic pathogenicity of P. gingivalis-S. gordonii communities arises from upregulation
of genes controlled by the RprY response regulator, including sufBCD which encode Fe-S clusters important in
resistance to oxidative stress and oxidative killing in neutrophils.
The Aims of the project are thus to 1) Characterize the P. gingivalis tyrosine kinase/phosphatase signaling axis.
In vitro and in vivo mutational approaches will be adopted to decipher the operational mode of the P. gingivalis
tyrosine kinase Ptk1, and the molecular basis of control of signal transduction. 2) Characterize tyrosine cross-
phosphorylation of the RprY response regulator in P. gingivalis. The functional consequences of tyrosine
phosphorylation of RprY, and the integration of this response regulator into the streptococcal induced signaling
hub, will be determined. 3) Determine the role of the Suf complex of P. gingivalis in polymicrobial synergy. The
role of the RprY-controlled suf genes in mediating resistance to neutrophil killing and determining polymicrobial
synergy in the murine alveolar bone loss model will be established.
Successful completion of this project will provide fundamental novel information regarding the regulation of
synergistic pathogenicity displayed by P. gingivalis and S. gordonii, which could ultimately be translated into
therapeutic strategies designed to target the community-based pathogenesis that underlies periodontal disease.

## Key facts

- **NIH application ID:** 9912645
- **Project number:** 5R01DE012505-23
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Richard J Lamont
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,750
- **Award type:** 5
- **Project period:** 1998-09-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912645

## Citation

> US National Institutes of Health, RePORTER application 9912645, Molecular Aspects of Oral Plaque Formation (5R01DE012505-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9912645. Licensed CC0.

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