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

Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis
Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis
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 ?-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.
0892-6638
286-295
Laver, J.R.
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Stevanin, T.M.
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Messenger, S.L.
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Lunn, A.D.
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Lee, M.E.
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Moir, J.W.B.
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Poole, R.K.
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Read, R.C.
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Laver, J.R.
ffb1b2f8-867c-43df-a5fc-a75340de21bc
Stevanin, T.M.
374b0292-99a0-451a-924f-ca76749a91e5
Messenger, S.L.
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Lunn, A.D.
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Lee, M.E.
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Moir, J.W.B.
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Poole, R.K.
9539c68a-f185-4dad-bbce-8c2598333b8a
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Laver, J.R., Stevanin, T.M., Messenger, S.L., Lunn, A.D., Lee, M.E., Moir, J.W.B., Poole, R.K. and Read, R.C. (2010) Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis. The FASEB Journal, 24 (1), 286-295. (doi:10.1096/fj.08-128330). (PMID:19720623)

Record type: Article

Abstract

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 ?-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.

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More information

e-pub ahead of print date: 31 August 2009
Published date: January 2010
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 341694
URI: http://eprints.soton.ac.uk/id/eprint/341694
ISSN: 0892-6638
PURE UUID: a9290475-cfd9-44a4-91a3-f1b56548bcd5
ORCID for R.C. Read: ORCID iD orcid.org/0000-0002-4297-6728

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Date deposited: 06 Aug 2012 10:42
Last modified: 15 Mar 2024 03:42

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Contributors

Author: J.R. Laver
Author: T.M. Stevanin
Author: S.L. Messenger
Author: A.D. Lunn
Author: M.E. Lee
Author: J.W.B. Moir
Author: R.K. Poole
Author: R.C. Read ORCID iD

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