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

TY - JOUR

T1 - Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis

AU - Laver, Jay R.

AU - Stevanin, Tania M.

AU - Messenger, Sarah L.

AU - Lunn, Amy Dehn

AU - Lee, Margaret E.

AU - Moir, James W. B.

AU - Poole, Robert K.

AU - Read, Robert C.

PY - 2010/1

Y1 - 2010/1

N2 - S-nitrosylation 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 enterica and Escherichia coli, which serve to protect the microorganism from nitrosative stress within the intracellular environment. In this study, we demonstrate that expression of meningococcal NorB increases the rate at which low-molecular-weight S-nitrosothiol (SNO) decomposes in vitro. To determine whether this effect occurs in cells during infection by bacteria, we induced SNO formation in murine macrophages by activation with lipopolysaccharide and gamma-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., Stevanin, 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

AB - S-nitrosylation 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 enterica and Escherichia coli, which serve to protect the microorganism from nitrosative stress within the intracellular environment. In this study, we demonstrate that expression of meningococcal NorB increases the rate at which low-molecular-weight S-nitrosothiol (SNO) decomposes in vitro. To determine whether this effect occurs in cells during infection by bacteria, we induced SNO formation in murine macrophages by activation with lipopolysaccharide and gamma-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., Stevanin, 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

KW - S-nitrosylation

KW - infection

KW - macrophage

KW - nitrosative stress

KW - ENTERICA SEROVAR TYPHIMURIUM

KW - COLI FLAVOHAEMOGLOBIN HMP

KW - NEISSERIA-MENINGITIDIS

KW - ESCHERICHIA-COLI

KW - FLAVOHEMOGLOBIN HMP

KW - NITROSATIVE STRESS

KW - HUMAN MACROPHAGES

KW - SALMONELLA FLAVOHEMOGLOBIN

KW - SKELETAL-MUSCLE

KW - REPRESSOR NSRR

UR - http://www.scopus.com/inward/record.url?scp=75149137411&partnerID=8YFLogxK

U2 - 10.1096/fj.08-128330

DO - 10.1096/fj.08-128330

M3 - Article

SN - 0892-6638

VL - 24

SP - 286

EP - 295

JO - The FASEB Journal

JF - The FASEB Journal

IS - 1

ER -