Nitric oxide modulates bacterial biofilm formation through a multicomponent cyclic-di-GMP signaling network.

Plate L, Marletta MA
Mol Cell. 2012 46 (4): 449-60

PMID: 22542454 · PMCID: PMC3361614 · DOI:10.1016/j.molcel.2012.03.023

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (20)

3',5'-Cyclic-GMP Phosphodiesterases Amino Acid Sequence Bacterial Proteins Biofilms Cyclic GMP Gammaproteobacteria Guanylate Cyclase Histidine Kinase Models, Biological Molecular Sequence Data Nitric Oxide Phosphorylation Protein Kinases Protein Structure, Tertiary Receptors, Cytoplasmic and Nuclear Second Messenger Systems Sequence Homology, Amino Acid Shewanella Signal Transduction Soluble Guanylyl Cyclase

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