Arginine metabolism as a mutualistic strategy in the interaction between Porphyromonas gingivalis and Filifactor alocis.

Metabolic cross-feeding is a main driver of microbial mutualism under various stresses. Elevated arginine levels in the periodontal microenvironment reshape pathogen physiology. Here, we discovered that increased arginine levels disrupted the intracellular amino acid metabolism of the periodontal pathogen Porphyromonas gingivalis by repressing glutamate dehydrogenase activity and α-ketoglutarate production via the accumulation of NH3. This perturbation inhibited P. gingivalis growth and was accompanied by increased expression of the PorX/PorY-associated T9SS and enhanced small-peptide acquisition. Given the frequent co-occurrence of P. gingivalis and Filifactor alocis in periodontitis, our findings suggested that F. alocis partially relieved arginine-associated growth inhibition of P. gingivalis through ArcA-dependent arginine degradation, thereby promoting its persistence under high-arginine conditions. This cooperative arginine metabolism is critical for the resilience of microbial communities and may serve as a therapeutic target.