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Start Over Descriptor "methionine salvage" Journal infection and immunity
2 results on '"methionine salvage"'

1. Methylthioadenosine Suppresses Salmonella Virulence

Author

Jeffrey S, Bourgeois, Daoguo, Zhou, Teresa L M, Thurston, James J, Gilchrist, and Dennis C, Ko

Subjects
Salmonella typhimurium, Adenosine, Genomic Islands, Virulence Factors, methylthioadenosine, flagellar motility, Mice, Methionine, Bacterial Proteins, Salmonella, Polyamines, Animals, Salmonella Infections, Animal, SPI-1, Virulence, methionine salvage, Gene Expression Regulation, Bacterial, Molecular Pathogenesis, Mice, Inbred C57BL, Repressor Proteins, Disease Models, Animal, metJ, Flagella, inflammation, virulence regulation, metabolism
Abstract

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., 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.

Published
2018

2. Methylthioadenosine Suppresses Salmonella Virulence.

Author

Bourgeois JS, Zhou D, Thurston TLM, Gilchrist JJ, and Ko DC

Subjects
Adenosine analogs & derivatives, Animals, Bacterial Proteins genetics, Disease Models, Animal, Flagella, Gene Expression Regulation, Bacterial, Genomic Islands, Mice, Mice, Inbred C57BL, Polyamines metabolism, Repressor Proteins genetics, Salmonella Infections, Animal microbiology, Virulence drug effects, Virulence Factors genetics, Adenosine metabolism, Methionine metabolism, Salmonella typhimurium pathogenicity
Abstract

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 Δ metJ 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 Δ metJ had reduced virulence in oral and intraperitoneal infection of C57BL/6J mice independently of the effects of MTA on SPI-1. Finally, Δ metJ 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., (Copyright © 2018 Bourgeois et al.)

Published
2018
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