 but the effects of MTA on Salmonella virulence remain unknown.

Previously, our labs determined that MTA plays a multifaceted role in Salmonella infection. We originally identified MTA to be a positive regulator of host cell pyroptosis, a rapid, proinflammatory form of cell death, during Salmonella infection ([@B16]). More recently, we showed that host MTA is released into plasma during *S*. Typhimurium infection and that high plasma MTA levels are associated with poor sepsis outcomes in humans ([@B17]). Paradoxically, we showed that treatment of mice with exogenous MTA suppresses sepsis-associated cytokines and extends the life span of mice infected with a lethal dose of *S*. Typhimurium ([@B17]). While this finding was consistent with previous reports that MTA acts as an anti-inflammatory molecule ([@B18][@B19][@B20]), it was in contrast to our findings that MTA primes cells to undergo pyroptosis. Together, these data led us to hypothesize that increased extracellular concentrations of MTA could potentially have independent effects on both the host and the pathogen during infection.

Here we show that fluctuations in MTA levels regulate *S*. Typhimurium virulence *in vitro* and *in vivo*. Treatment of *S*. Typhimurium with exogenous MTA prior to infection or increasing endogenous bacterial production of MTA through genetic deletion of the methionine regulon suppressor, *metJ*, reduced the induction of pyroptosis and invasion *in vitro*. Furthermore, we report that both Δ*metJ* mutants and MTA-treated bacteria demonstrate transcriptional, translational, and functional reductions in motility and SPI-1 activity. Finally, we found that Δ*metJ* mutants have reduced virulence *in vivo* and that disrupting the methionine metabolism pathway in the bacteria can influence the inflammatory state of the host. Together, these data reveal the importance of MTA and bacterial methionine metabolism in regulating *S*. Typhimurium virulence and host inflammation and provide a possible example of host-pathogen metabolite cross 