March 28, 2013
Chemistry Department, SUNY Stony Brook
Nitric oxide signaling in bacteria: Discovery of a new mechanism for regulating bacterial biofilms
The ability of biological systems to sense and respond to external stimuli is of fundamental importance. Dissolved gases such as nitric oxide (NO), carbon monoxide (CO) and molecular oxygen (O2) are increasingly recognized as important biological signals. For example, in eukaryotes, NO is well established as a signaling molecule that mediates functions such as smooth muscle relaxation, neuronal signal transduction, and inhibition of platelet aggregation. Recent evidence has suggested that NO also serves a signaling role in bacteria, being linked to processes such as quorum sensing and biofilm formation. Biofilms are surface-bound, matrix-encapsulated, multicellular communities that are extremely resistant to antibiotic treatments. In addition to being important in many naval, industrial, and environmental processes, biofilms are responsible for ~60% of all human infections. Despite the well-documented role of NO in this process, the mechanism for NO regulation of biofilm formation has not been established. Protein-bound porphyrin groups typically serve gas-sensing roles and thus we hypothesized that the H-NOX (heme nitric oxide/oxygen binding domain) family may contribute to biofilm regulation in bacteria. H-NOX domains are evolutionarily conserved gas-sensing heme domains that include the well-characterized eukaryotic NO sensor, soluble guanylate cyclase. In the genomes of bacteria, H-NOX genes are typically co-cistronic with either a diguanylate cyclase (DGC) or histidine kinase (HK) gene. Both DGCs and HKs are linked to biofilm regulation. Evidence from biochemical and biophysical characterization of proteins in the H-NOX signaling pathway as well as proteomic, genetic, and growth studies will be presented to support our hypothesis. Furthermore, we have established a role for heme distortion in regulating downstream signal transduction by H-NOX.