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Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Parvimonas micra exacerbates periodontitis by infiltrating host cells through TmpC and circumventing lysosomal
Zixuan Li1, Pingping Wang2, Haiting Gao2
1Department of Human Microbiome & Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China; Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
Background:
Periodontitis poses a significant threat to human oral health, and microorganisms serving as the initiating factor in its pathogenesis. Parvimonas micra (P. micra), a Gram-positive anaerobic bacterium prevalent within the oral cavities of patients with periodontitis, remains underexplored in terms of its full contribution to periodontitis pathogenesis.
Methods:
16S rRNA sequencing was performed on human gingival crevicular fluid samples, whilst micro-CT was used in experimental rat models to assess the impact of P. micra on periodontitis progression. Single-cell RNA sequencing was employed to examine dynamic alterations in rat periodontal cell composition and the enrichment of gene pathways during P. micra infection. Finally, His pull-down assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify key virulence factors of P. micra and host cell receptors.
Findings:
In this study, we examined the abundance of P. micra in gingival crevicular fluid and validated its pathogenic potential in vivo. Single-cell RNA sequencing revealed that P. micra disrupted the periodontal immune and mineralisation microenvironment. Further investigation showed that P. micra manipulated its surface adhesins to bind receptors on periodontal ligament stem cells, activating the intracellular NF-κB and ERK1/2 signalling pathways and impairing osteogenic activity. Finally, we identified a mechanism by which P. micra employed a surface protein to evade autophagic clearance, thereby facilitating immune escape.
Interpretation:
This study identifies P. micra as a pivotal periodontal pathogen, and the elucidation of its molecular mechanisms provides potential therapeutic targets for periodontitis and related systemic conditions.
Funding:
This work was supported by the National Natural Science Foundation of China (No. 82270980, 82071122), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0501400), Taishan TePin Scientist Project of Shandong Province (tstp20250546), the Natural Science Foundation of Jiangsu Province (No. BK20240268), High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University (No. 0024C035), Shandong Provincial Key Research and Development Program (Competitive Innovation Platform, 2025CXPT042), the Major Innovation Projects in Shandong Province (No. 2021SFGC0502), and the Shandong Province Key Research and Development Program (No. 2021ZDSYS18).
Insights
Parvimonas micra is a key pathogen in periodontitis, disrupting the oral environment and immune defenses. Understanding its mechanisms offers new therapeutic targets for treating this common oral disease.
Area of Science:
- Oral microbiology and immunology
- Periodontal disease pathogenesis
- Bacterial virulence factors
Background:
- Periodontitis is a major oral health concern driven by microbial factors.
- Parvimonas micra (P. micra), a common oral bacterium, has an incompletely understood role in periodontitis.
- Investigating P. micra's specific contributions to disease progression is crucial.
Purpose of the Study:
- To elucidate the pathogenic mechanisms of Parvimonas micra in periodontitis.
- To identify virulence factors and host cell interactions of P. micra.
- To explore P. micra's impact on the periodontal microenvironment and immune response.
Main Methods:
- 16S rRNA sequencing of gingival crevicular fluid.
- Micro-computed tomography (micro-CT) in rat models.
- Single-cell RNA sequencing (scRNA-seq) for cellular and pathway analysis.
- His pull-down assays and LC-MS/MS for virulence factor identification.
Main Results:
- P. micra abundance correlated with periodontitis.
- scRNA-seq revealed P. micra disrupts periodontal immune and mineralization.
- P. micra adhesins bind to periodontal ligament stem cells, activating NF-κB/ERK1/2 pathways and impairing osteogenesis.
- P. micra utilizes surface proteins to evade autophagy and escape immune detection.
Conclusions:
- P. micra is identified as a pivotal pathogen in periodontitis.
- Elucidation of P. micra's molecular mechanisms provides potential therapeutic targets.
- This research contributes to understanding periodontitis and related systemic conditions.
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