# Probing Polymicrobial Synergy Using High Throughput Genomics

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $557,465

## 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 that initiates and drives the disease. In vivo
imaging studies have shown that oral microbial communities are highly structured; however, little is known
regarding the mechanisms that control spatial orientation within communities or the role of spatial structure in
pathogenicity. Our ongoing studies have identified and quantified key spatial parameters in synergistic
communities of the periodontal pathogen Aggregatibacter actinomycetemcomitans with S. gordonii. In this
proposal, we will characterize the molecular basis and biological relevance of spatial parameters controlling the
association of P. gingivalis with its community partners. In the first Aim, we will focus on the interaction between
P. gingivalis and S. gordonii, a molecularly well-characterized process resulting in elevated pathogenicity of the
dual species communities. We will determine the spatial parameters that define the dual species communities
and their impact on pathogenicity. Further, through the use of specific mutants, we will assess the impact of
known community virulence factors and communication mechanisms on spatial orientation. In the second Aim,
we will use Tn-seq and RNA-seq genomic approaches to holistically assess the fitness determinants and
transcriptome patterns which control spatial patterning in P. gingivalis and S. gordonii. We will prioritize potential
contributors to metabolic synergy for further study of the relationship between spatial proximity and interspecies
communication. In the third aim, we will explore Pg genetic pathways important for fitness during infection with
a diverse set of co-infecting bacteria. The application of these focused and comprehensively based approaches
will allow us to integrate key spatial parameters with molecular interspecies interactions in the context of
community pathogenic potential. Successful completion of this project will provide fundamental information
regarding the development and regulation of synergistic pathogenicity displayed by spatially defined
polymicrobial communities which could ultimately be translated into therapeutic strategies designed to target the
community-based pathogenesis that underlies periodontal disease.

## Key facts

- **NIH application ID:** 10177998
- **Project number:** 5R01DE023193-09
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Richard J Lamont
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $557,465
- **Award type:** 5
- **Project period:** 2013-07-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177998

## Citation

> US National Institutes of Health, RePORTER application 10177998, Probing Polymicrobial Synergy Using High Throughput Genomics (5R01DE023193-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10177998. Licensed CC0.

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