Cobalamin serves as a key redox-active mediator, protecting Porphyromonas gingivalis from oxidative stress.

Cobalamin (vitamin B12) is critical for bacterial adaptation and pathogenesis, aiding redox management during host defenses, including reactive oxygen species (ROS). Periodontal pathogens, such as Porphyromonas gingivalis (Pg), rely on homologs of the Btu transporter for cobalamin uptake, but the mechanisms and impact remain largely unexplored. This study investigates how cobalamin uptake via the Pg Btu transporter regulates stress responses and pathogenesis. Preliminary data demonstrate that cobalamin enhances Pg's survival under oxidative stress, promotes biofilm formation, and upregulates virulence factors like gingipains. we hypothesize that cobalamin can provide a powerful tier of stress response regulation during Pg pathogenesis through a homolog of the Btu (cobalamin) transporter by which Pg uptakes cobalamin and utilizes it to resist oxidative stress and promote pathogenesis. This grant proposal aims to reveal the mechanisms underlying cobalamin uptake by the Pg Btu transporter and its role in resistance to oxidative stress and pathogenesis. This hypothesis will be investigated through two specific aims. Aim 1. The impact of the Pg Btu cobalamin transporter on resistance to oxidative stress. Investigate the role of the PGN_0704 (btu) gene in cobalamin uptake under Hĸ2Oĸ2 stress using gene expression analysis and knockout mutants. Aim 2. Understanding the impact of cobalamin uptake on Pg pathogenesis and virulence potential. Examine how cobalamin uptake via the Btu transporter influences gingipain activity and the colonization and invasion potential of Pg using an in vitro cell model. The results will yield essential insights into the molecular mechanisms of cobalamin-mediated pathoadaptations in strictly anaerobic pathogens.