# Folate-Modulated Virulence of Porphyromonas gingivalis

> **NIH NIH F32** · UNIVERSITY OF LOUISVILLE · 2022 · $68,382

## Abstract

Periodontal disease, one of the most common infections of humans, is driven by pathogens that influence the
composition and trajectory of the oral polymicrobial community. These pathogens can take hold in an inhospitable
environment and pave the way for other organism to colonize and grow. A key factor in allowing a pathogen to
establish itself and colonize despite these odds is successfully regulating the expression of virulence factors
while acquiring enough essential nutrition for replication and growth. One such essential nutrient is folate, which
is classically linked to modulation of virulence in microbes. Although the literature has shown that limiting folate
availability leads to decreased virulence in many microbes, however, we have found a clear exception to this
rule in the periodontal pathogen P. gingivalis, an asaccharolytic organism that uses an amino-acid based
metabolism. As a model for studying how folate availability regulates virulence in asaccharolytic pathogens, we
are investigating how restricting the ability of P. gingivalis to produce folate regulates its expression of virulence
factors. The objectives of this study are to: i) define the metabolic phenotype of P. gingivalis induced by folate
deficiency; ii) determine how the metabolic phenotype of P. gingivalis is associated with the expression of
virulence factors; and iii) characterize the host immune response to folate-deficient P. gingivalis. The completion
of this study will provide critical insight into how limiting folate availability does not universally suppress the
virulence of pathogens, but has the potential to result in enhanced virulence in asaccharolytic pathogens. We
will also provide novel information on how the flux of metabolites in the folate and one-carbon metabolic pathways
are associated with virulence in P. gingivalis and how this could apply to other organisms utilizing non-carbohydrate based metabolisms. Our overall long-term goal is to apply these findings to refine when it is
appropriate to use antifolates to treat microbial infections and reduce overall harm caused to patients. Further,
these findings will help narrow down alternative pathways to target treatments for infections caused by
asaccharolytic pathogens.

## Key facts

- **NIH application ID:** 10491743
- **Project number:** 5F32DE031493-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Kendall Stocke
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $68,382
- **Award type:** 5
- **Project period:** 2021-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491743

## Citation

> US National Institutes of Health, RePORTER application 10491743, Folate-Modulated Virulence of Porphyromonas gingivalis (5F32DE031493-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10491743. Licensed CC0.

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