Oxysulfur and organosulfur toxins: the hidden mediators of the oral-systemic connection.

The oral cavity hosts complex microbial communities whose pathogenic members are implicated in systemic diseases, including cardiovascular, metabolic, and neurodegenerative disorders. While proteinaceous virulence factors and inflammatory pathways have been extensively studied, the contribution of microbial sulfur chemistry to the oral-systemic connection remains poorly understood. Here, we report Raman spectroscopic evidence that two major oral pathogens, Streptococcus mutans and Porphyromonas gingivalis, actively exploit oxysulfur/organosulfur molecules as part of their pathogenic arsenal. In the former bacterium, the protein referred to as Collagen binding mutans (Cnm) protein, exhibits a high density of organosulfur-related vibrational signatures, consistent with the presence of chemically reactive sulfur moieties that may promote extracellular matrix adhesion and oxidative stress modulation. In parallel, the latter bacterium selectively enriches its outer membrane vesicles with oxysulfur-associated molecular species, suggesting a vesicle-mediated delivery mechanism for sulfur-based toxins to host cells. These findings point to a convergent strategy whereby chemically aggressive organosulfur and oxysulfur compounds function as molecular effectors at host-pathogen interfaces. By framing sulfur chemistry as a functional dimension of microbial virulence, this study provides a new chemical perspective on the oral-systemic connection and highlights Raman spectroscopy as a powerful tool for uncovering noncanonical pathogenic mechanisms at the molecular scale.