title: Nitric oxide modulates bacterial biofilm formation through a multicomponent cyclic-di-GMP signaling network.
abstract: Nitric oxide (NO) signaling in vertebrates is well characterized and involves the heme-nitric oxide/oxygen-binding (H-NOX) domain of soluble guanylate cyclase as a selective NO sensor. In contrast, little is known about the biological role or signaling output of bacterial H-NOX proteins. Here, we describe a molecular pathway for H-NOX signaling in Shewanella oneidensis. NO stimulates biofilm formation by controlling the levels of the bacterial secondary messenger cyclic diguanosine monophosphate (c-di-GMP). Phosphotransfer profiling was used to map the connectivity of a multicomponent signaling network that involves integration from two histidine kinases and branching to three response regulators. A feed-forward loop between response regulators with phosphodiesterase domains and phosphorylation-mediated activation intricately regulated c-di-GMP levels. Phenotypic characterization established a link between NO signaling and biofilm formation. Cellular adhesion may provide a protection mechanism for bacteria against reactive and damaging NO. These results are broadly applicable to H-NOX-mediated NO signaling in bacteria.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Plate
authors.forename: Michael A
authors.initials: MA
authors.lastname: Marletta
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D020563:Gammaproteobacteria / Q000235:genetics / Q000502:physiology; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000071677:Histidine Kinase; D008954:Models, Biological; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D017386:Sequence Homology, Amino Acid; D020592:Shewanella / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase
chemical_list: D001426:Bacterial Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; C062025:bis(3',5')-cyclic diguanylic acid; D011494:Protein Kinases; D000071677:Histidine Kinase; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP