Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium.
Production of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3206869?pdf=render |
| _version_ | 1818269062807945216 |
|---|---|
| author | Luisa A Denkel Sarah A Horst Syed Fazle Rouf Vera Kitowski Oliver M Böhm Mikael Rhen Timo Jäger Franz-Christoph Bange |
| author_facet | Luisa A Denkel Sarah A Horst Syed Fazle Rouf Vera Kitowski Oliver M Böhm Mikael Rhen Timo Jäger Franz-Christoph Bange |
| author_sort | Luisa A Denkel |
| collection | DOAJ |
| description | Production of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such oxidative damage, methionine sulfoxide reductases MsrA and MsrB are known to reduce MetSOs, the former being specific for the S-form and the latter being specific for the R-form. However, at present the role of methionine sulfoxide reductases in the pathogenesis of intracellular bacterial pathogens has not been fully detailed. Here we show that deletion of msrA in the facultative intracellular pathogen Salmonella (S.) enterica serovar Typhimurium increased susceptibility to exogenous H(2)O(2), and reduced bacterial replication inside activated macrophages, and in mice. In contrast, a ΔmsrB mutant showed the wild type phenotype. Recombinant MsrA was active against free and peptidyl Met-S-SO, whereas recombinant MsrB was only weakly active and specific for peptidyl Met-R-SO. This raised the question of whether an additional Met-R-SO reductase could play a role in the oxidative stress response of S. Typhimurium. MsrC is a methionine sulfoxide reductase previously shown to be specific for free Met-R-SO in Escherichia (E.) coli. We tested a ΔmsrC single mutant and a ΔmsrBΔmsrC double mutant under various stress conditions, and found that MsrC is essential for survival of S. Typhimurium following exposure to H(2)O(2,) as well as for growth in macrophages, and in mice. Hence, this study demonstrates that all three methionine sulfoxide reductases, MsrA, MsrB and MsrC, facilitate growth of a canonical intracellular pathogen during infection. Interestingly MsrC is specific for the repair of free methionine sulfoxide, pointing to an important role of this pathway in the oxidative stress response of Salmonella Typhimurium. |
| first_indexed | 2024-12-12T20:48:25Z |
| format | Article |
| id | doaj.art-fdd11039b22c418f9548e3c6b0b27080 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T20:48:25Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fdd11039b22c418f9548e3c6b0b270802022-12-22T00:12:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2697410.1371/journal.pone.0026974Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium.Luisa A DenkelSarah A HorstSyed Fazle RoufVera KitowskiOliver M BöhmMikael RhenTimo JägerFranz-Christoph BangeProduction of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such oxidative damage, methionine sulfoxide reductases MsrA and MsrB are known to reduce MetSOs, the former being specific for the S-form and the latter being specific for the R-form. However, at present the role of methionine sulfoxide reductases in the pathogenesis of intracellular bacterial pathogens has not been fully detailed. Here we show that deletion of msrA in the facultative intracellular pathogen Salmonella (S.) enterica serovar Typhimurium increased susceptibility to exogenous H(2)O(2), and reduced bacterial replication inside activated macrophages, and in mice. In contrast, a ΔmsrB mutant showed the wild type phenotype. Recombinant MsrA was active against free and peptidyl Met-S-SO, whereas recombinant MsrB was only weakly active and specific for peptidyl Met-R-SO. This raised the question of whether an additional Met-R-SO reductase could play a role in the oxidative stress response of S. Typhimurium. MsrC is a methionine sulfoxide reductase previously shown to be specific for free Met-R-SO in Escherichia (E.) coli. We tested a ΔmsrC single mutant and a ΔmsrBΔmsrC double mutant under various stress conditions, and found that MsrC is essential for survival of S. Typhimurium following exposure to H(2)O(2,) as well as for growth in macrophages, and in mice. Hence, this study demonstrates that all three methionine sulfoxide reductases, MsrA, MsrB and MsrC, facilitate growth of a canonical intracellular pathogen during infection. Interestingly MsrC is specific for the repair of free methionine sulfoxide, pointing to an important role of this pathway in the oxidative stress response of Salmonella Typhimurium.http://europepmc.org/articles/PMC3206869?pdf=render |
| spellingShingle | Luisa A Denkel Sarah A Horst Syed Fazle Rouf Vera Kitowski Oliver M Böhm Mikael Rhen Timo Jäger Franz-Christoph Bange Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium. PLoS ONE |
| title | Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium. |
| title_full | Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium. |
| title_fullStr | Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium. |
| title_full_unstemmed | Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium. |
| title_short | Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium. |
| title_sort | methionine sulfoxide reductases are essential for virulence of salmonella typhimurium |
| url | http://europepmc.org/articles/PMC3206869?pdf=render |
| work_keys_str_mv | AT luisaadenkel methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium AT sarahahorst methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium AT syedfazlerouf methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium AT verakitowski methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium AT olivermbohm methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium AT mikaelrhen methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium AT timojager methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium AT franzchristophbange methioninesulfoxidereductasesareessentialforvirulenceofsalmonellatyphimurium |