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Methylthioadenosine Suppresses Salmonella Virulence
- Source :
- Infection and Immunity
- Publication Year :
- 2018
-
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.<br />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.
- 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
Subjects
Details
- ISSN :
- 10985522
- Volume :
- 86
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Infection and immunity
- Accession number :
- edsair.pmid..........4bf7af492965148fdc190b0b3a5da6e5