Parvimonas micra exacerbates periodontitis by infiltrating host cells through TmpC and circumventing lysosomal elimination via AppA.

Abstract

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).