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Filifactor alocis FtxA-dependent suppression of inflammation and apoptosis

ABSTRACT: Filifactor alocis is regarded as an emerging oral pathogen with roles in the etiology of periodontal, peri-implantitis, and endodontic infections. It was recently discovered that approximately 50% of known strains of this organism encode and express a Repeats-in-Toxin (RTX) protein, FtxA. This potential toxin appears to be associated with both progress and severity of periodontal disease. Mechanism(s) how FtxA may promote periodontitis are not yet known but could be linked to an enhanced proliferation of F. alocis in ftxA-positive strains. In the present work, we have investigated possible mechanistic correlations based on the activity of FtxA, as present in bacterial whole cells, in association with extracellular vesicles, and as a recombinant protein, exploiting macrophage-like THP-1 cells as a model. For this, we have used the ftxA-expressing strain, ATCC 35896, and F. alocis 148B-17U, which naturally lacks the gene encoding FtxA. Using RNA-Seq and cytokine array analysis we have pinpointed a role of FtxA in shifting the host response towards immunosuppression, also inhibiting apoptosis, immune cell recruitment, and with a potential role as well in downregulating mitochondrial and oxidative phosphorylation pathways in the THP-1 cells. Such role(s) in immune suppression could provide a plausible explanation why FtxA is associated with the progress and severity of periodontal disease, and further studies on mechanistic interactions between FtxA and host cells might therefore reveal novel potential therapeutic targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311337 | GEO | 2026/03/25

REPOSITORIES: GEO

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Project description:BackgroundBacteria in periodontal pockets develop complex sessile communities that attach to the tooth surface. These highly dynamic microfloral environments challenge both clinicians and researchers alike. The exploration of structural organisation and bacterial interactions within these biofilms is critically important for a thorough understanding of periodontal disease. In recent years, Filifactor alocis, a fastidious, Gram-positive, obligately anaerobic rod was repeatedly identified in periodontal lesions using DNA-based methods. It has been suggested to be a marker for periodontal deterioration. The present study investigated the epidemiology of F. alocis in periodontal pockets and analysed the spatial arrangement and architectural role of the organism in in vivo grown subgingival biofilms.ResultsA species-specific oligonucleotide probe, FIAL, was designed and evaluated. A total of 490 subgingival plaque samples were submitted to PCR and subsequent dot blot hybridization to compare the prevalence of F. alocis in patients suffering from generalized aggressive periodontitis (GAP), chronic periodontitis (CP), and control subjects resistant to periodontitis. Moreover, a specially designed carrier system was used to collect in vivo grown subgingival biofilms from GAP patients. Subsequent topographic analysis was performed using fluorescence in situ hybridization.While the majority of patients suffering from GAP or CP harboured F. alocis, it was rarely detected in the control group. In the examined carrier-borne biofilms the organism predominantly colonized apical parts of the pocket in close proximity to the soft tissues and was involved in numerous structures that constitute characteristic architectural features of subgingival periodontal biofilms.ConclusionsF. alocis is likely to make a relevant contribution to the pathogenetic structure of biofilms accounting for periodontal inflammation and can be considered an excellent marker organism for periodontal disease.

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Filifactor alocis FtxA-dependent suppression of inflammation and apoptosis

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