# The Role of Glutamine Metabolism for P. gingivalis-Induced Non-Canonical Autophagy in Epithelial Cells

> **NIH NIH F31** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $47,552

## Abstract

Growing evidence underlines that Glutamine (Gln) metabolism can influence key metabolic and autophagic
cellular events. Porphyromonas gingivalis (P.g) is a major periodontopathic, fastidious, pathobiont and
successful colonizer of gingival mucosa, which has recently been identified to induce a special form of
autophagy in human gingival epithelial cells (GECs). While GECs function as an intrinsically important first line
of immune defense of the gingiva, GECs can be exploited by P.g for securing a successful persistence niche in
the oral mucosa and a potential systemic dissemination route. Despite the growing evidence pinpointing that
altered Gln metabolism can contribute to cellular pathologies, knowledge gaps remain regarding how host Gln
metabolism could be influenced by bacteria to regulate host redox homeostasis and potentially promote
bacterial survival in the GECs. Recently, we discovered that P.g steadily increases robust Glutathione (GSH)
production in GECs to combat host-mediated oxidative stress-driven pathogen clearance. Our novel findings,
for the first time, show that P.g infection alters host Gln metabolism, a component of GSH synthesis, in GECs.
In addition, we recently demonstrated that P.g induces a pro-bacterial form of autophagy in GECs, where
Endoplasmic Reticulum-rich (ER)/Microtubule-associated protein 1A/1B-light chain 3 (LC3) double membrane
autophagosomes act as replicative niches for P.g and protect the bacteria from antimicrobial degradation
pathways. Our novel data shows that the biogenesis and maintenance of these P.g-containing
autophagosomes is dependent on the critical redox molecule, Glutathione Peroxidase 1 (GpX1). The
dependency on GpX1 can be markedly altered by increasing free Gln levels in GECs' cellular environment.
Thus, our overarching hypothesis for this proposal is that P.g alters host Gln metabolism in GECs to
maintain host redox homeostasis and specifically contributes to the biogenesis of a GpX1-driven, pro-bacterial
form of autophagy. Two Specific Aims are proposed to test this hypothesis. Aim 1 will characterize the
phenotypic molecular events occurring during P.g infection that specifically associate with host cell Gln
metabolism and the host cell redox state, allowing for the intracellular survival of P.g in GECs. Aim 2 will
mechanistically determine the molecular interactome involved in P.g-induced autophagy through the
modulation of host Gln metabolism in GECs. These collectively will identify what elements of the Gln metabolic
pathways are critical for the autophagic survival of P.g in GECs, and will elucidate the specific molecular
machineries involved in pro-bacterial autophagy driven by changes in host Gln metabolism upon P.g infection.
Overall, this proposal will contribute to the identification of novel targeted therapeutic strategies to control the
chronic intracellular colonization of P.g in the oral mucosa and beyond. Receiving the F31 Fellowship for this
proposal will further the appl...

## Key facts

- **NIH application ID:** 10537625
- **Project number:** 1F31DE032273-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Bridgette Frances Wellslager
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $47,552
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537625

## Citation

> US National Institutes of Health, RePORTER application 10537625, The Role of Glutamine Metabolism for P. gingivalis-Induced Non-Canonical Autophagy in Epithelial Cells (1F31DE032273-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10537625. Licensed CC0.

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