# Microbial sphingolipids and suppression of host inflammation in periodontal disease

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $574,891

## Abstract

PROJECT SUMMARY
Eukaryotic SLs are the basic building blocks of cell membranes and serve as key signaling molecules.
Bacterial synthesis of SLs is poorly understood, and almost entirely restricted to the phylum Bacteroidetes.
These microbes are generally considered symbionts of mammalian hosts. Although microbe-elicited chronic
dysregulated inflammation is central feature of soft and hard tissue destruction and periodontal disease
pathogenesis, this inflammation is, paradoxically, insufficient to clear the source of infection. Thus, subversion
of host immunity is central to the chronic nature of this disease. Research has shown that Porphyromonas
gingivalis, a member of the Bacteroidetes is uniquely capable of targeted and dynamic immune suppression,
yet little is known of the underlying mechanisms. Remarkably, our studies have illuminated the importance of
P. gingivalis SL in regulating the elicited host immune response to this organism and we have shown that
these SLs are transferred from this organism and incorporated into host cells – putatively understood as an
interkingdom communication system. The overarching hypothesis of the research we propose is that synthesis
of SLs affords P. gingivalis and possibly other oral Bacteroidetes a mechanism of immune regulation.
Specifically, our published and preliminary studies have determined that P. gingivalis secretes SL-containing
outer membrane vesicles (OMVs) that elicit only mild inflammation compared to OMVs from a P. gingivalis
mutant incapable of synthesizing SLs, and that the phosphoglycerol-dihydrocerimides (a subset of SLs)
containing OMVs are particularly adept at immune suppression. We are proposing that SL-OMVs are an
exquisite delivery system that forms the basis of a mechanism of P. gingivalis-host communication to control
inflammation. The goal of our proposed studies is to determine how P. gingivalis SLs contribute to OMV cargo
loading and subsequently how these SL-OMVs modulate the host innate inflammatory response. We will
interrogate host sensing of P. gingivalis SL-OMVs both in vitro and in vivo. As early innate immune responses
control host responses at mucosal surfaces such as the oral cavity, we will employ unique genetically modified
P. gingivalis strains, and OMVs isolated from these strains to determine which OMV-components are involved
in suppression. Molecular, immunologic, imaging, and transcriptomic, and biochemical techniques will be
deployed to elucidate the underlying functions of SL-OMVs and mechanisms of host innate signaling. Lastly,
we will use oral bone loss modelling to examine the virulence of P. gingivalis strains that are altered in the
synthesis of SLs. The rationale for these studies is that identifying immunoregulatory mechanisms used by
oral pathogens will provide prime targets for the development of therapeutic strategies. Thus, the long-term
goal of this research program is to elucidate the mechanisms underlying SL-mediated OMV delivered immune
suppres...

## Key facts

- **NIH application ID:** 10435569
- **Project number:** 5R01DE031159-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Mary Ellen Davey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $574,891
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435569

## Citation

> US National Institutes of Health, RePORTER application 10435569, Microbial sphingolipids and suppression of host inflammation in periodontal disease (5R01DE031159-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10435569. Licensed CC0.

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