2026 CHEMISTRY RESEARCH DAY - POSTERS/CONTRIBUTORS

NosP as a Heme–Nitric Oxide Switch Controlling Bacterial Biofilm Behavior

Bacterial biofilms contribute to chronic and hospital-acquired infections because they are highly resistant to antibiotics and host defenses. My research seeks to understand how bacteria sense environmental signals and translate them into decisions to form, maintain, or disperse biofilms. A major focus has been nitric oxide (NO), a small signaling molecule that can trigger profound changes in bacterial community behavior. Our work established molecular connections between NO sensing, cyclic-di-GMP signaling, and quorum sensing, and led to the discovery of NosP, a broadly conserved family of heme-based NO sensors found in many bacteria.

Our recent studies reveal that NosP is regulated not simply by NO, but by the interplay between heme binding and NO coordination. In Pseudomonas aeruginosa, apo-NosP is relatively dynamic and does not strongly inhibit its partner histidine kinase, NahK. Heme binding stabilizes NosP, promotes tighter interaction with NahK, and strongly inhibits kinase activity. In contrast, NO coordination to heme-bound NosP reverses much of this stabilization, weakens the NosP–NahK interaction, and partially restores NahK activity. These observations support a model in which heme and NO act as opposing molecular inputs that remodel NosP structure and thereby tune downstream signaling.

NahK is embedded within the highly interconnected GacS multikinase network and regulates biofilm architecture, motility, quorum sensing, virulence-associated metabolites, denitrification, NO homeostasis, and stress adaptation. Together, our work suggests that the NosP–NahK module functions as a molecular switch through which P. aeruginosa integrates heme availability, NO, respiration, nutrient status, and quorum-sensing information to transition among persistent, virulent, motile, and dispersal-associated states.