# Dissecting the role of sialic acid and sialidase in the pathophysiology of Porphyromonas gingivalis

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $479,423

## Abstract

The overarching goal of this application is to investigate the role of sialidase and sialic acid in the keystone
pathogen Porphyromonas gingivalis (Pg) and their contributions to the pathogenesis of periodontitis. Sialic acid
(SA), a group of structurally related nine-carbon sugar acids, plays critical roles in host-pathogen interactions.
On the host side, mammalian mucosal surfaces and secretions of the mouth, airway, gut, and vagina are
especially sialoglycan-rich, which have a variety of biological, biophysical, antimicrobial, and immunological
functions. In addition, a number of cell surface receptors (e.g., chemokine-, immunoglobulin-, and toll-like-
receptors) are either sialylated or recognize sialylated ligands, which play critical roles in immune recognition
and activation. On the pathogen side, many bacterial pathogens have evolved different mechanisms to target
host SA for adherence, invasion, immune modulation and nutrient acquisition, thereby promoting their fitness
and pathogenesis. Specifically, bacterial pathogens often use sialidases to hydrolyze host sialoglycans,
compromise host immune defenses, and promote their survival in the mucosal niche. Salivary and gingival
crevicular fluids contain a high concentration of SA bound to sialoglycans in various proteins such as mucins.
Clinical studies indicate that sialidase activity in the oral cavity is positively associated with the severity of
periodontitis; thus, it is recommended as a biomarker for periodontitis diagnosis. Accordingly, sialidases have
been found in numerous oral bacteria including the keystone pathogen Porphyromonas gingivalis (Pg). Pg
lacks genes to synthesize SA. Instead, it encodes a sialidase (PG0352), which is highly conserved among all
genome sequenced Pg isolates. Previous studies from our group and others have shown that PG0352 plays a
crucial role in Pg capsule synthesis, biofilms, stress response, innate immune responses, and virulence.
However, the molecular mechanism underlying these phenotypes remains elusive. In this application, we
hypothesize that Pg employs a sialidase and a SA specific transporter to scavenge host SA, which is in turn
used to modify Pg cell surface molecules such as capsule and lipopolysaccharide (LPS), thereby intercepting
host innate immune defenses, such as complement killing and phagocytosis of neutrophils and macrophage. To
test this hypothesis, the following studies are specifically designed and will be implemented: Aim 1: To delineate
the biochemical and structural features of PG0352 by using an approach of genetics, biochemistry, and
crystallography; Aim 2: To investigate how Pg imports and utilizes SA by using a multidisciplinary approach of
genetics, biochemistry, glycobiology, immunology, and biofilm assays; and Aim 3: To elucidate the role of
PG0352 in the pathogenicity of Pg by using various in vitro and in vivo approaches. Completion of this project
will not only provide mechanistic insights into understanding the rol...

## Key facts

- **NIH application ID:** 10758291
- **Project number:** 5R01DE030667-04
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Chunhao Chris Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $479,423
- **Award type:** 5
- **Project period:** 2021-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758291

## Citation

> US National Institutes of Health, RePORTER application 10758291, Dissecting the role of sialic acid and sialidase in the pathophysiology of Porphyromonas gingivalis (5R01DE030667-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10758291. Licensed CC0.

---

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