Colouring dysbiosis: FetB-dependent Mn-PPIX produced by Porphyromonas gingivalis shapes the oral microbiota

Polymicrobial diseases, such as periodontitis, are shaped by microbial interactions and nutrient‑responsive metabolic adaptations. Here, we identify novel porphyrin pigments produced by Porphyromonas gingivalis in response to haemoglobin concentrations resembling those found in the gingival sulcus and periodontal pocket. Under these conditions, P. gingivalis develops a distinctive pink, highly fluorescent phenotype. Spectroscopic and mass‑spectrometric analyses revealed the accumulation of protoporphyrin IX (PPIX), manganese‑substituted PPIX (Mn‑PPIX), and haem. Deletion of the haemin‑binding protein gene fetB greatly reduced Mn‑PPIX production and fluorescence, whereas complementation restored both. Structural and biochemical characterisation demonstrated that FetB shares homology with bacterial metal chelatases and catalyses the insertion of metal ions into tetrapyrrole rings. Mn‑PPIX exhibited selective antimicrobial activity against several oral bacteria, including Streptococcus mitis, Streptococcus salivarius, Enterococcus faecalis, and oral Lactobacillus species, while other streptococci were resistant. These findings indicate that P. gingivalis modulates porphyrin metabolism in response to host‑derived haemoglobin, producing extracellular pigments with selective antimicrobial properties that may shape the oral community and promote dysbiosis. Targeting Mn‑PPIX production or limiting haemoglobin availability may offer new strategies to restore microbial balance and mitigate disease progression.