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Methylthioadenosine Suppresses Salmonella Virulence
In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously, we showed a transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) concentration in serum during systemic Salmonella...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105896/ https://www.ncbi.nlm.nih.gov/pubmed/29866910 http://dx.doi.org/10.1128/IAI.00429-18 |
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author | Bourgeois, Jeffrey S. Zhou, Daoguo Thurston, Teresa L. M. Gilchrist, James J. Ko, Dennis C. |
author_facet | Bourgeois, Jeffrey S. Zhou, Daoguo Thurston, Teresa L. M. Gilchrist, James J. Ko, Dennis C. |
author_sort | Bourgeois, Jeffrey S. |
collection | PubMed |
description | In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously, we showed a transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) concentration in serum during systemic Salmonella enterica serovar Typhimurium infection. Here we explored the functional consequences of increased MTA concentrations on S. Typhimurium virulence. We found that MTA, but not other related metabolites involved in polyamine synthesis and methionine salvage, reduced motility, host cell pyroptosis, and cellular invasion. Further, we developed a genetic model of increased bacterial endogenous MTA production by knocking out the master repressor of the methionine regulon, metJ. Like MTA-treated S. Typhimurium, the ΔmetJ mutant displayed reduced motility, host cell pyroptosis, and invasion. These phenotypic effects of MTA correlated with suppression of flagellar and Salmonella pathogenicity island 1 (SPI-1) networks. S. Typhimurium ΔmetJ had reduced virulence in oral and intraperitoneal infection of C57BL/6J mice independently of the effects of MTA on SPI-1. Finally, ΔmetJ bacteria induced a less severe inflammatory cytokine response in a mouse sepsis model. Together, these data indicate that exposure of S. Typhimurium to MTA or disruption of the bacterial methionine metabolism pathway suppresses S. Typhimurium virulence. |
format | Online Article Text |
id | pubmed-6105896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-61058962018-08-31 Methylthioadenosine Suppresses Salmonella Virulence Bourgeois, Jeffrey S. Zhou, Daoguo Thurston, Teresa L. M. Gilchrist, James J. Ko, Dennis C. Infect Immun Molecular Pathogenesis In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously, we showed a transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) concentration in serum during systemic Salmonella enterica serovar Typhimurium infection. Here we explored the functional consequences of increased MTA concentrations on S. Typhimurium virulence. We found that MTA, but not other related metabolites involved in polyamine synthesis and methionine salvage, reduced motility, host cell pyroptosis, and cellular invasion. Further, we developed a genetic model of increased bacterial endogenous MTA production by knocking out the master repressor of the methionine regulon, metJ. Like MTA-treated S. Typhimurium, the ΔmetJ mutant displayed reduced motility, host cell pyroptosis, and invasion. These phenotypic effects of MTA correlated with suppression of flagellar and Salmonella pathogenicity island 1 (SPI-1) networks. S. Typhimurium ΔmetJ had reduced virulence in oral and intraperitoneal infection of C57BL/6J mice independently of the effects of MTA on SPI-1. Finally, ΔmetJ bacteria induced a less severe inflammatory cytokine response in a mouse sepsis model. Together, these data indicate that exposure of S. Typhimurium to MTA or disruption of the bacterial methionine metabolism pathway suppresses S. Typhimurium virulence. American Society for Microbiology 2018-08-22 /pmc/articles/PMC6105896/ /pubmed/29866910 http://dx.doi.org/10.1128/IAI.00429-18 Text en Copyright © 2018 Bourgeois et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Molecular Pathogenesis Bourgeois, Jeffrey S. Zhou, Daoguo Thurston, Teresa L. M. Gilchrist, James J. Ko, Dennis C. Methylthioadenosine Suppresses Salmonella Virulence |
title | Methylthioadenosine Suppresses Salmonella Virulence |
title_full | Methylthioadenosine Suppresses Salmonella Virulence |
title_fullStr | Methylthioadenosine Suppresses Salmonella Virulence |
title_full_unstemmed | Methylthioadenosine Suppresses Salmonella Virulence |
title_short | Methylthioadenosine Suppresses Salmonella Virulence |
title_sort | methylthioadenosine suppresses salmonella virulence |
topic | Molecular Pathogenesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105896/ https://www.ncbi.nlm.nih.gov/pubmed/29866910 http://dx.doi.org/10.1128/IAI.00429-18 |
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