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Flavohemoglobin Hmp protects Salmonella enterica serovar typhimurium from nitric oxide-related killing by human macrophages

Flavohemoglobin Hmp protects Salmonella enterica serovar typhimurium from nitric oxide-related killing by human macrophages
Flavohemoglobin Hmp protects Salmonella enterica serovar typhimurium from nitric oxide-related killing by human macrophages

Survival of macrophage microbicidal activity is a prerequisite for invasive disease caused by the enteric pathogen Salmonella enterica serovar Typhimurium. Flavohemoglobins, such as those of Escherichia coli, Salmonella, and yeast, play vital roles in protection of these microorganisms in vitro from nitric oxide (NO) and nitrosative stress. A Salmonella hmp mutant defective in flavohemoglobin (Hmp) synthesis exhibits growth that is hypersensitive to nitrosating agents. We found that respiration of this mutant exhibited increased inhibition by NO, whereas wild-type cells pregrown with sodium nitroprusside or S-nitrosoglutathione showed enhanced tolerance of NO. Most significantly, hmp mutants internalized by primary human peripheral monocyte-derived macrophages survived phagocytosis relatively poorly compared with similarly bound and internalized wild-type cells. That the enhanced sensitivity to macrophage microbicidal activity is due primarily to the failure of Salmonella to detoxify NO was suggested by the ability of L-N(G)-monomethyl arginine-an inhibitor of NO synthase-to eliminate the difference in killing between wild-type and hmp mutant Salmonella cells. These observations suggest that Salmonella Hmp contributes to protection from NO-mediated inhibition by human macrophages.

Bacterial Adhesion, Bacterial Proteins, Cells, Cultured, Hemeproteins, Humans, Macrophages, Mutagenesis, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Phagocytosis, Salmonella typhimurium, Journal Article, Research Support, Non-U.S. Gov't
0019-9567
4399-405
Stevanin, Tânia M
ff5fc52c-a001-42d6-9b01-3cb24e4758b1
Poole, Robert K
5f1f3b79-cf45-4ae6-89cd-e4259c03ae56
Demoncheaux, Eric A G
772bb5e6-00a2-4558-90bb-3d9a76f6eb30
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Stevanin, Tânia M
ff5fc52c-a001-42d6-9b01-3cb24e4758b1
Poole, Robert K
5f1f3b79-cf45-4ae6-89cd-e4259c03ae56
Demoncheaux, Eric A G
772bb5e6-00a2-4558-90bb-3d9a76f6eb30
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Stevanin, Tânia M, Poole, Robert K, Demoncheaux, Eric A G and Read, Robert C (2002) Flavohemoglobin Hmp protects Salmonella enterica serovar typhimurium from nitric oxide-related killing by human macrophages. Infection and Immunity, 70 (8), 4399-405. (doi:10.1128/IAI.70.8.4399-4405.2002).

Record type: Article

Abstract

Survival of macrophage microbicidal activity is a prerequisite for invasive disease caused by the enteric pathogen Salmonella enterica serovar Typhimurium. Flavohemoglobins, such as those of Escherichia coli, Salmonella, and yeast, play vital roles in protection of these microorganisms in vitro from nitric oxide (NO) and nitrosative stress. A Salmonella hmp mutant defective in flavohemoglobin (Hmp) synthesis exhibits growth that is hypersensitive to nitrosating agents. We found that respiration of this mutant exhibited increased inhibition by NO, whereas wild-type cells pregrown with sodium nitroprusside or S-nitrosoglutathione showed enhanced tolerance of NO. Most significantly, hmp mutants internalized by primary human peripheral monocyte-derived macrophages survived phagocytosis relatively poorly compared with similarly bound and internalized wild-type cells. That the enhanced sensitivity to macrophage microbicidal activity is due primarily to the failure of Salmonella to detoxify NO was suggested by the ability of L-N(G)-monomethyl arginine-an inhibitor of NO synthase-to eliminate the difference in killing between wild-type and hmp mutant Salmonella cells. These observations suggest that Salmonella Hmp contributes to protection from NO-mediated inhibition by human macrophages.

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More information

Published date: August 2002
Keywords: Bacterial Adhesion, Bacterial Proteins, Cells, Cultured, Hemeproteins, Humans, Macrophages, Mutagenesis, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Phagocytosis, Salmonella typhimurium, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416552
URI: http://eprints.soton.ac.uk/id/eprint/416552
ISSN: 0019-9567
PURE UUID: 5a5a2297-8017-40e4-b65b-d022f45067a3
ORCID for Robert C Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 21 Dec 2017 17:30
Last modified: 10 Nov 2021 03:30

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Contributors

Author: Tânia M Stevanin
Author: Robert K Poole
Author: Eric A G Demoncheaux
Author: Robert C Read ORCID iD

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