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Updated: Aug 18, 2026
Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Lipopolysaccharide preparation extracted from Porphyromonas gingivalis lipoprotein-deficient mutant shows a marked
Yasuyuki Asai1, Masahito Hashimoto, Hansel M Fletcher
1Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan.
Abstract:
We recently demonstrated that a new PG1828-encoded lipoprotein (PG1828LP) was able to be separated from a Porphyromonas gingivalis lipopolysaccharide (LPS) preparation, and we found that it exhibited strong cell activation, similar to that of Escherichia coli LPS, through a Toll-like receptor 2 (TLR2)-dependent pathway. In order to determine the virulence of PG1828LP toward cell activation, we generated a PG1828-deficient mutant of P. gingivalis strain 381 by allelic exchange mutagenesis using an ermF-ermAM antibiotic resistance cassette. A highly purified preparation of LPS from a PG1828-deficient mutant (DeltaPG1828-LPS) showed nearly the same ladder-like patterns in silver-stained gels as a preparation of LPS from a wild-type strain (WT-LPS), as well as Limulus amoebocyte lysate activities that were similar to those of the WT-LPS preparation. However, the ability of the DeltaPG1828-LPS preparation to activate NF-kappaB in TLR2-expressing cells was markedly attenuated. Cytokine production by human gingival fibroblasts was also decreased in response to the DeltaPG1828-LPS preparation in comparison with the WT-LPS preparation, and the activity was comparable to the stimulation of highly purified lipid A of P. gingivalis by TLR4. Further, lethal toxicity was rarely observed following intraperitoneal injection of the PG1828-deficient mutant into mice compared to that with the wild-type strain, while the DeltaPG1828-LPS preparation showed no lethal toxicity. Taken together, these results clearly indicate that PG1828LP plays an essential role in inflammatory responses and may be a major virulence factor of P. gingivalis.
Insights
A novel lipoprotein (PG1828LP) from Porphyromonas gingivalis is a key virulence factor. Removing it significantly reduces inflammatory responses and lethal toxicity, highlighting its role in disease.
Area of Science:
- Microbiology
- Immunology
- Oral Health
Background:
- Porphyromonas gingivalis is a key pathogen in periodontitis.
- Lipopolysaccharide (LPS) from P. gingivalis activates immune cells via Toll-like receptors (TLRs).
- A previously unidentified lipoprotein (PG1828LP) was found to contribute to LPS-induced cell activation.
Purpose of the Study:
- To investigate the role of PG1828LP in P. gingivalis virulence and immune cell activation.
- To determine if PG1828LP is a major virulence factor.
- To elucidate the contribution of PG1828LP to inflammatory responses.
Main Methods:
- Generation of a PG1828-deficient mutant of P. gingivalis using allelic exchange mutagenesis.
- Purification and characterization of LPS from wild-type and mutant strains.
- Assessment of NF-kappaB activation in TLR2-expressing cells.
- Measurement of cytokine production by human gingival fibroblasts.
- Evaluation of lethal toxicity in a mouse model.
Main Results:
- LPS from the PG1828-deficient mutant (DeltaPG1828-LPS) showed attenuated NF-kappaB activation via TLR2 compared to wild-type LPS (WT-LPS).
- Cytokine production by gingival fibroblasts was decreased by DeltaPG1828-LPS.
- The PG1828-deficient mutant exhibited significantly reduced lethal toxicity in mice compared to the wild-type strain.
- DeltaPG1828-LPS preparation showed no lethal toxicity.
Conclusions:
- PG1828LP is essential for potent inflammatory responses mediated by P. gingivalis.
- PG1828LP is identified as a major virulence factor of P. gingivalis.
- Targeting PG1828LP may offer a therapeutic strategy against P. gingivalis infections.
