Abstract
Nitric oxide (NO) is a toxic gas encountered by bacteria as a product of their own metabolism or as a result of a host immune response. Non-toxic concentrations of NO have been shown to initiate changes in bacterial behaviors such as the transition between planktonic and biofilm-associated lifestyles. The heme nitric oxide/oxygen binding proteins (H-NOX) are a widespread family of bacterial heme-based NO sensors that regulate biofilm formation in response to NO. The presence of H-NOX in several human pathogens combined with the importance of planktonic–biofilm transitions to virulence suggests that H-NOX sensing may be an important virulence factor in these organisms. Here we review the recent data on H-NOX NO signaling pathways with an emphasis on H-NOX homologs from pathogens and commensal organisms. The current state of the field is somewhat ambiguous regarding the role of H-NOX in pathogenesis. However, it is clear that H-NOX regulates biofilm in response to environmental factors and may promote persistence in the environments that serve as reservoirs for these pathogens. Finally, the evidence that large subgroups of H-NOX proteins may sense environmental signals besides NO is discussed within the context of a phylogenetic analysis of this large and diverse family.
Highlights
Oxidative and nitrosative stress are encountered by virtually every organism, and mechanisms to sense and ameliorate these stresses are essential to survival
heme nitric oxide/oxygen binding protein (H-NOX) proteins directly influence the activity of these enzymes, while in others they bind and regulate histidine kinases (HKs) that modulate diguanylate cyclase (DGC)/PDE activity through phosphorylation
H-NOX can interact directly with DGC/PDE enzymes, inhibiting the DGC functionality and/or stimulating PDE activity resulting in a decrease in c-di-GMP concentrations and a dissolution of biofilm in response to Nitric oxide (NO) (Figure 1A)
Summary
The heme nitric oxide/oxygen binding proteins (H-NOX) are a widespread family of bacterial heme-based NO sensors that regulate biofilm formation in response to NO. The presence of H-NOX in several human pathogens combined with the importance of planktonic–biofilm transitions to virulence suggests that H-NOX sensing may be an important virulence factor in these organisms. We review the recent data on H-NOX NO signaling pathways with an emphasis on H-NOX homologs from pathogens and commensal organisms. It is clear that H-NOX regulates biofilm in response to environmental factors and may promote persistence in the environments that serve as reservoirs for these pathogens. The evidence that large subgroups of H-NOX proteins may sense environmental signals besides NO is discussed within the context of a phylogenetic analysis of this large and diverse family.
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