Methylthioadenosine Suppresses Salmonella Virulence.
Jeffrey S BourgeoisDaoguo ZhouTeresa L M ThurstonJames J GilchristDennis C KoPublished in: Infection and immunity (2018)
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.
Keyphrases
- listeria monocytogenes
- biofilm formation
- escherichia coli
- pseudomonas aeruginosa
- staphylococcus aureus
- antimicrobial resistance
- candida albicans
- signaling pathway
- single cell
- cystic fibrosis
- cell therapy
- drug induced
- acute kidney injury
- type diabetes
- machine learning
- amino acid
- metabolic syndrome
- genome wide
- early onset
- gene expression
- high glucose
- stem cells
- dna methylation
- newly diagnosed
- deep learning