Bacterial nitric oxide detoxification prevents host cell S‐nitrosothiol formation: a novel mechanism of bacterial pathogenesis

Snitrosylation is an important mediator of multiple nitric oxide‐dependent biological processes, including eukaryotic cellular events such as macrophage apoptosis and proinflammatory signaling. Many pathogenic bacteria possess NO detoxification mechanisms, such as the nitric oxide reductase (NorB) of Neisseria meningitidis and the flavohemoglobins (Hmp) of Salmonella entérica and Escherichia coli, which serve to protect the microorganism from nitrosative stress within the in‐tracellular environment. In this study, we demonstrate that expression of meningococcal NorB increases the rate at which low‐molecular‐weight S ‐nitrosothiol (SNO) de‐composes in vitro. To determine whether this effect occurs in cells during infection by bacteria, we induced SNO formation in murine macrophages byactivation with lipopolysaccharide and ‐/‐interferon and observed a reduced abundance of SNO during coincubation with N. meningitidis, S. enterica, or E. coli. In each case, this effect was shown to be dependent on bacterial NO detoxification genes, which act to prevent SNO formation through the removal of NO. This may represent a novel mechanism of host cell injury by bacteria.—Laver, J. R., Steva‐nin, T. M., Messenger, S. L., Dehn Lunn, A., Lee, M. E., Moir, J. W. B., Poole, R. K., Read, R. C. Bacterial nitric oxide detoxification prevents host cell S‐nitrosothiol formation: a novel mechanism of bacterial pathogenesis. FASEB J . 24, 286–295 (2010). www.fasebj.org