Nitric Oxide Regulation of H-NOX Signaling Pathways in Bacteria

Nisbett, Lisa-Marie; Boon, Elizabeth M.

doi:10.1021/acs.biochem.6b00754

Cited by 33 publications

(53 citation statements)

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“…7 NO-ligated H-NOX effectively regulates cyclic di-GMP and histidine kinase signaling pathways in a variety of bacterial species; H-NOX proteins have been reviewed extensively. 8–10 …”

Section: Introductionmentioning

confidence: 99%

Spectral Characterization of a Novel NO Sensing Protein in Bacteria: NosP

et al. 2018

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A novel family of bacterial hemoproteins named NosP has been discovered recently; its members are proposed to function as nitric oxide (NO) responsive proteins involved in bacterial group behaviors such as quorum sensing and biofilm growth and dispersal. Currently, little is known about molecular activation mechanisms in NosP. Here, functional studies were performed utilizing the distinct spectroscopic characteristics associated with the NosP heme cofactor. NosPs from Pseudomonas aeruginosa (Pa), Vibrio cholerae (Vc) and Legionella pneumophila (Lpg) were studied in their ferrous-unligated forms as well as their ferrous-CO, ferrous-NO, and ferric-CN adducts. The resonance Raman (rR) data collected on the ferric forms strongly support the existence of a distorted heme-cofactor, which is a common feature in NO sensors. The ferrous spectra exhibit a 213 cm−1 feature, which is assigned to the Fe-Nhis stretching mode. The Fe-C and C-O frequencies in the spectra of ferrous-CO NosP complexes are inversely correlated with relatively similar frequencies, consistent with a proximal histidine ligand and a relatively hydrophobic environment. The rR spectra obtained for isotopically labeled ferrous-NO adducts provide evidence of formation of a 5-coordinate NO complex, resulting from proximal Fe-Nhis cleavage, which is believed to play a role in biological heme-NO signal transduction. Additionally, we found that of the three NosPs studied, Lpg NosP contains the most electropositive ligand binding pocket, while Pa NosP has the most electronegative ligand binding pocket. This pattern is also observed in the measured heme reduction potentials for these three proteins, which may indicate distinct functions for each.

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“…7 NO-ligated H-NOX effectively regulates cyclic di-GMP and histidine kinase signaling pathways in a variety of bacterial species; H-NOX proteins have been reviewed extensively. 8–10 …”

Section: Introductionmentioning

confidence: 99%

Spectral Characterization of a Novel NO Sensing Protein in Bacteria: NosP

et al. 2018

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“…nitric oxide | denitrification | protein-protein complex | NOR | NiR N itric oxide (NO) is a diffusible radical gas molecule that has been recognized as an integral signaling molecule in eukaryotes and bacteria (1,2). NO plays pivotal roles in vasodilation, smooth muscle relaxation, neurotransmission, and the immune system in mammals.…”

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confidence: 99%

“…In mammals, NO activates an NO receptor, soluble guanylate cyclase (sGC), upon the binding to heme in sGC, which induces the formation of signaling molecule, cGMP, from GTP. Currently, an NO binding protein homologous to the heme domain of sGC is thought to participate in bacterial NO signaling pathways (2). However, NO is a highly cytotoxic gas and easily reacts with biomolecules, despite its essential function.…”

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confidence: 99%

Dynamics of nitric oxide controlled by protein complex in bacterial system

Terasaka

Yamada

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Nitric oxide (NO) plays diverse and significant roles in biological processes despite its cytotoxicity, raising the question of how biological systems control the action of NO to minimize its cytotoxicity in cells. As a great example of such a system, we found a possibility that NO-generating nitrite reductase (NiR) forms a complex with NOdecomposing membrane-integrated NO reductase (NOR) to efficiently capture NO immediately after its production by NiR in anaerobic nitrate respiration called denitrification. The 3.2-Å resolution structure of the complex of one NiR functional homodimer and two NOR molecules provides an idea of how these enzymes interact in cells, while the structure may not reflect the one in cells due to the membrane topology. Subsequent all-atom molecular dynamics (MD) simulations of the enzyme complex model in a membrane and structure-guided mutagenesis suggested that a few interenzyme salt bridges and coulombic interactions of NiR with the membrane could stabilize the complex of one NiR homodimer and one NOR molecule and contribute to rapid NO decomposition in cells. The MD trajectories of the NO diffusion in the NiR:NOR complex with the membrane showed that, as a plausible NO transfer mechanism, NO released from NiR rapidly migrates into the membrane, then binds to NOR. These results help us understand the mechanism of the cellular control of the action of cytotoxic NO.is a diffusible radical gas molecule that has been recognized as an integral signaling molecule in eukaryotes and bacteria (1, 2). NO plays pivotal roles in vasodilation, smooth muscle relaxation, neurotransmission, and the immune system in mammals. In bacteria, NO is also involved in several biological processes such as biofilm formation, quorum sensing, and symbiosis. NO is synthesized from L-arginine by an enzyme called nitric oxide synthase (NOS). In mammals, NO activates an NO receptor, soluble guanylate cyclase (sGC), upon the binding to heme in sGC, which induces the formation of signaling molecule, cGMP, from GTP. Currently, an NO binding protein homologous to the heme domain of sGC is thought to participate in bacterial NO signaling pathways (2). However, NO is a highly cytotoxic gas and easily reacts with biomolecules, despite its essential function. Thus, regulation of the cellular action of NO is crucial.Some bacteria would be exposed to large amounts of NO during denitrification, which implies that the control of NO dynamics is indispensable to minimize the cytotoxic effects of NO in such bacteria. Denitrification is a form of microbial anaerobic respiration by bacteria living in oxygen-limited environments in which the sequential reduction of nitrate to dinitrogen (NO 3 − → NO 2 − → NO → N 2 O → N 2 ) is coupled to bioenergy production. Denitrification is also crucial for the survival of some pathogenic bacteria inside host cells (3, 4). For example, Pseudomonas aeruginosa is a major opportunistic pathogen that survives through denitrification in hypoxic and anoxic environments such as the lungs of cystic fibros...

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“…Indeed, several of these H-NOX/cyclic di-GMP systems have been biochemically characterized, and to varying extents, also biologically characterized, including those from the bacteria Legionella pneumophila , 73 Shewanella woodyi , 57,58,60 Shewanella oneidensis , 74 and Agrobacterium vitis . 48 Interestingly, in some of these species, NO-bound H-NOX appears to promote biofilm formation, while in other species, it appears to suppress biofilm formation. Specifically, in L. pneumophila and S. oneidensis , NO signaling through H-NOX is reported to enhance biofilm formation, while in S. woodyi and A. vitis , NO signaling through H-NOX disperses biofilms.…”

Section: Nitric Oxide and H-nox Signaling In Bacterial Biofilmsmentioning

confidence: 99%

“…All of these NO and H-NOX-mediated cyclic di-GMP signaling pathways have been previously reviewed, 27,47,48 so we direct the readers to those reviews for more detailed information on the studies described here.…”

Section: Nitric Oxide and H-nox Signaling In Bacterial Biofilmsmentioning

confidence: 99%

Discovery of Two Bacterial Nitric Oxide-Responsive Proteins and Their Roles in Bacterial Biofilm Regulation

2017

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CONSPECTUS Bacterial biofilms form when bacteria adhere to a surface and produce an exopolysaccharide matrix (Costerton et al. Science 1999, 284, 1318; Davies et al. Science 1998, 280, 295; Flemming et al. Nat. Rev. Microbiol. 2010, 8, 623). Because biofilms are resistant to antibiotics, they are problematic in many aspects of human health and welfare, causing, for instance, persistent fouling of medical implants such as catheters and artificial joints (Brunetto et al. Chimia 2008, 62, 249). They are responsible for chronic infections in the lungs of cystic fibrosis patients and in open wounds, such as those associated with burns and diabetes. They are also a major contributor to hospital-acquired infections (Sievert et al. Infec. Control Hosp. Epidemiol. 2013, 34, 1; Tatterson et al. Front. Biosci. 2001, 6, D890). It has been hypothesized that effective methods of biofilm control will have widespread application (Landini et al. Appl. Microbiol. Biotechnol. 2010, 86, 813). A promising strategy is to target the mechanisms that drive biofilm dispersal, because dispersal results in biofilm removal and in the restoration of antibiotic sensitivity. First documented in Nitrosomonas europaea (Schmidt et al. J. Bacteriol. 2004, 186, 2781) and the cystic fibrosis-associated pathogen Pseudomonas aeruginosa (Barraud et al. J. Bacteriol. 2006, 188, 7344; J. Bacteriol. 2009, 191, 7333), regulation of biofilm formation by nanomolar levels of the diatomic gas nitric oxide (NO) has now been documented in numerous bacteria (Barraud et al. Microb. Biotechnol. 2009, 2, 370; McDougald et al. Nat. Rev. Microbiol. 2012, 10, 39; Arora et al. Biochemistry 2015, 54, 3717; Barraud et al. Curr. Pharm. Des. 2015, 21, 31). NO-mediated pathways are, therefore, promising candidates for biofilm regulation. Characterization of the NO sensors and NO-regulated signaling pathways should allow for rational manipulation of these pathways for therapeutic applications. Several laboratories, including our own, have shown that a class of NO sensors called H-NOX (heme-nitric oxide or oxygen binding domain) affects biofilm formation by regulating intracellular cyclic di-GMP concentrations and quorum sensing (Arora et al. Biochemistry 2015, 54, 3717; Plate et al. Trends Biochem. Sci. 2013, 38, 566; Nisbett et al. Biochemistry 2016, 55, 4873). Many bacteria that respond to NO do not encode an hnoX gene, however. My laboratory has now discovered an additional family of bacterial NO sensors, called NosP (nitric oxide sensing protein). Importantly, NosP domains are widely conserved in bacteria, especially Gram-negative bacteria, where they are encoded as fusions with or in close chromosomal proximity to histidine kinases or cyclic di-GMP synthesis or phosphodiesterase enzyme, consistent with signaling. In this Account, we briefly review NO and HNOX signaling in bacterial biofilms, describe our discovery of the NosP family, and provide support for its role in biofilm regulation in Pseudomonas aeruginosa, Vibrio cholerae, Legionella pneumophila, and Shewanella o...

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Nitric Oxide Regulation of H-NOX Signaling Pathways in Bacteria

Cited by 33 publications

References 88 publications

Spectral Characterization of a Novel NO Sensing Protein in Bacteria: NosP

Spectral Characterization of a Novel NO Sensing Protein in Bacteria: NosP

Dynamics of nitric oxide controlled by protein complex in bacterial system

Discovery of Two Bacterial Nitric Oxide-Responsive Proteins and Their Roles in Bacterial Biofilm Regulation

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