Filifactor alocis FtxA-dependent suppression of inflammation and apoptosis

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.