Methylthioadenosine Suppresses Salmonella Virulence

Area of Science:

• Microbiology
• Molecular Biology
• Infectious Diseases

Background:

• Microbes utilize metabolite signals to regulate virulence factor deployment.
• Elevated serum methylthioadenosine (MTA) was previously observed during systemic Salmonella Typhimurium infection.

Purpose of the Study:

• To investigate the functional impact of increased MTA concentrations on Salmonella Typhimurium virulence.
• To explore the role of bacterial methionine metabolism in regulating virulence.

Main Methods:

• Treatment of Salmonella Typhimurium with MTA and related metabolites.
• Generation and analysis of a Salmonella Typhimurium ΔmetJ mutant.
• Assessment of bacterial motility, host cell pyroptosis, and invasion.
• Evaluation of flagellar and Salmonella pathogenicity island 1 (SPI-1) network activity.
• In vivo virulence studies in C57BL/6J mice (oral and intraperitoneal infection).
• Analysis of inflammatory cytokine response in a mouse sepsis model.

Main Results:

• MTA significantly reduced Salmonella Typhimurium motility, host cell pyroptosis, and invasion.
• The Salmonella Typhimurium ΔmetJ mutant exhibited similar phenotypic reductions as MTA-treated bacteria.
• These virulence reductions correlated with the suppression of flagellar and SPI-1 networks.
• The ΔmetJ mutant showed decreased virulence in mouse infection models.
• ΔmetJ bacteria elicited a less severe inflammatory cytokine response in a sepsis model.

Conclusions:

• Increased MTA levels or disruption of methionine metabolism suppresses Salmonella Typhimurium virulence.
• Methionine metabolism plays a critical role in regulating Salmonella virulence pathways.
• Targeting bacterial methionine metabolism could be a potential strategy to control Salmonella infections.