# Turning on Persistence: Novel Molecular Determinants that Underpin P. gingivalis Intracellular Survival In Epithelial Cells

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $357,438

## Abstract

A growing multidisciplinary evidence critically underpins that Porphyromonas gingivalis, a leading pathobiont of
the oral cavity that successfully remodels oral microbial communities to a pathophysiological state, can live in
concert with human gingival epithelial cells (GECs). Epithelial cells are emerged as an integrally important arm
of innate defenses in the oral mucosa, while recent observations suggest that these cells can be exploited as
privileged growth niches and a reservoir by P. gingivalis, which can intracellularly multiply and remain largely
unharmed in GECs. Despite, extensive systems level molecular knowledge exists on the P. gingivalis and GEC
interaction, there is considerably little known on the intracellular life of the organism in this central cell type. We
recently revealed that formation of autophagosomes is critical for the P. gingivalis' intracellular replication and
evasion of the anti-microbial degradation pathways in the GECs. Our novel preliminary findings also support
that lipidation of LC3-C, a key molecule in the `selective autophagy' pathway, which targets intracellular
pathogens is significantly modulated by P. gingivalis under the control of an anti-stress molecule, HSP27.
Further, glutathione peroxidase (GpX1), a major host redox balance enzyme and a regulator of autophagic flux
largely impacted on the global LC3 lipidation state of GECs upon infection. The inhibition of either HSP27 or
GpX1 appears to severely affect the intracellular trafficking and viability of the microorganism. The central
hypothesis is that P. gingivalis induces a distinct form of selective autophagy, which results in
protection of bacterial life and ultimately securing of P. gingivalis' persistence in the oral mucosa. To
test this novel hypothesis, we will pursue two-pronged approach, where we propose the selective autophagy
requires tightly coordinated actions of HSP27 and GpX1 to form autophagosomes that fully function as
protected replicative niches for P. gingivalis. Aim 1 will define the selective molecular machinery that drives P.
gingivalis-containing autophagosome assembly under the control of HSP27 and the mechanisms that disrupt
autophagic flux for the evasion of cellular degradation pathways. Aim 2 will establish the role of GpX1 in
regulating the selective autophagy in infection via redox homeostasis and suppressing autophagolysosomal
machinery. Both aims will employ reductionist primary GECs culture systems to functionally dissect out the
mechanisms and phenotypically characterize the molecular events and sub-cellular components. Aim 3 will
establish the dual significance of these two components using oral epithelial-tissue-specific knockout mice
models. Thus, this proposal aims to fill a significant gap in our fundamental knowledge that is how P.
gingivalis, a facultatively intracellular pathogen, establishes a privileged cellular environment and converts
nutritionally rich epithelial cells into potentially a central reserv...

## Key facts

- **NIH application ID:** 10137645
- **Project number:** 1R01DE030313-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** OZLEM YILMAZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,438
- **Award type:** 1
- **Project period:** 2020-09-10 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137645

## Citation

> US National Institutes of Health, RePORTER application 10137645, Turning on Persistence: Novel Molecular Determinants that Underpin P. gingivalis Intracellular Survival In Epithelial Cells (1R01DE030313-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137645. Licensed CC0.

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