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FEB 7: Elizabeth Boon – Chemistry Lecture Series

Discovery of Two Nitric Oxide-sensing Hemoproteins and Their Role in the Regulation of Bacterial Biofilms”

Elizabeth Boon
Associate Professor of Chemistry
Stony Brook University

Date:   Wednesday, February 7th
Time:   11:00 AM
Room:  Chemistry C121


Bacteria colonize most surfaces, forming multicellular, antibiotic-resistant, communities known as biofilms. Biofilms cause chronic infections and persistent biofouling of medical implants, marine vessels, and environmental sensors. Biofilm dispersal by nanomolar nitric oxide (NO) appears to be a general phenomenon, but fundamental questions remain concerning the identity of the NO sensor and mechanism of signal transduction. NO has been reported to disperse bacterial biofilms through regulation of intracellular cyclic-di-guanosine monophosphate (c-di-GMP) concentrations. C-di-GMP is a tightly regulated second messenger-signaling molecule that is tightly correlated with biofilm formation. H-NOX (heme-nitric oxide/oxygen binding) proteins are well known NO sensors in eukaryotes that are also conserved in many environmental and opportunistic pathogenic bacteria. Indeed, we have shown that NO/H-NOX signaling disperses bacterial biofilms through a mechanism consistent with c-di-GMP signaling. However, H-NOX proteins are not conserved in most human pathogens, even those for which the mechanism of action is known to involve c-di-GMP signaling. Therefore, an alternate NO sensor must also exist. We have identified an alternate NO sensor, a novel hemoprotein we named NosP (nitric oxide sensing protein). NosP domains are conserved in bacterial genomes, they bind NO, and are encoded as fusions with, or in close chromosomal proximity to, proteins annotated as c-di-GMP synthesis or hydrolysis enyzmes. Therefore we hypothesize that NO generally disperses bacterial biofilms through regulation of intracellular kinase cascades and/or c-di-GMP concentrations, but the sensor varies; both NosP and H-NOX can fill this role. Evidence from biochemical characterization of proteins in the NosP and H-NOX signaling pathways, as well as genetic and biofilm growth studies, will be presented to support our hypothesis.