# L-Arg availability affects the physiological state of porphyromonas gingivalis.

> **NIH NIH R01** · ADA FORSYTH INSTITUTE, INC. · 2022 · $467,899

## Abstract

Project Summary/Abstract
Many chronic inflammatory diseases, including periodontal infections, are biofilm-based pathologies mediated
by indigenous microbiota persisting within complex host-associated microbial communities. Determining the
environmental cues that direct the physiological state (commensal versus pathogenic state) of oral anaerobes,
is fundamental to development of therapeutic strategies for periodontal diseases. Recent studies indicate that
the pathogenic potential of the anaerobic bacterium Porphyromonas gingivalis is not solely dependent on its
ability to colonize and proliferate within the subgingival biofilm; its physiological state and its associations within
the microbial consortium are fundamental to development of pathology. The central hypothesis for this
application is that the availability of L-arginine is a key signal/substrate that impacts P. gingivalis surface
translocation, expression of virulence determinants, and biofilm formation. Studies have reported that the
levels of arginine increase 2-fold (from ~5µM to 10µM) in gingival crevicular fluid during periodontal disease.
The reason for this increase is not known but may reflect a decrease in metabolism by the microbial
community, a decrease in uptake by host cells, or an increase in bacterial arginine biosynthesis. One known
factor is the activity of the arginine - specific cysteine proteases (Arg-gingipains) produced by P. gingivalis,
along with its carboxypeptidase that releases the terminal arginine residues from peptides produced by Arg-
gingipains. Our analysis shows that both intracellular and extracellular accumulation of L-arginine has a
negative impact on P. gingivalis physiology, confirming that the levels of L-arginine are monitored and
controlled. Our studies have shown that under L-arginine deplete conditions, P. gingivalis down regulates
expression of fimbriae, inhibiting biofilm formation; and, in contrast, addition of L-arginine boosts fimbrial
expression and surface colonization. Thus, P. gingivalis adjusts its lifestyle in response to changes in
extracellular L-arginine. What remains unclear is the sensing and regulatory mechanisms that control this
change in physiology. The goal of this application is to determine how P. gingivalis controls extracellular and
intracellular arginine concentrations and in particular the effect of changes in arginine concentration on its
ability to surface translocate. Importantly, L-arginine is known to be an important modulator of the host immune
response to pathogens, so we posit that there is a delicate balance between host and pathogen responses to
arginine during disease progression and that P. gingivalis has evolved with the ability to sense and respond to
this key amino acid as a fundamental strategy for persistence. The rationale for these studies is that
identifying the signals that control colonization and the physiological state of oral pathogens will provide prime
targets for the development of therape...

## Key facts

- **NIH application ID:** 10693412
- **Project number:** 7R01DE024580-08
- **Recipient organization:** ADA FORSYTH INSTITUTE, INC.
- **Principal Investigator:** Mary Ellen Davey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $467,899
- **Award type:** 7
- **Project period:** 2022-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693412

## Citation

> US National Institutes of Health, RePORTER application 10693412, L-Arg availability affects the physiological state of porphyromonas gingivalis. (7R01DE024580-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693412. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*