*P* values, indicated at the top, for the number of CFU and IL-6 concentrations were calculated by an unpaired *t* test with Welch\'s correction. Because the TNF-α data are nonnormal, a Kolmogorov-Smirnov test was used to calculate the *P* value.](zii9990925020008){#F8}

DISCUSSION {#sec3}
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Here we report that exposing *S*. Typhimurium to exogenous MTA or increasing endogenous MTA production suppresses virulence *in vitro* and *in vivo*. This adds to a growing body of literature demonstrating that environmental factors can regulate critical Salmonella virulence factors ([@B3][@B4][@B7], [@B52], [@B53]). We found that MTA can suppress both SPI-1 and the flagellar regulon *in vitro*, as well as currently unidentified virulence factors *in vivo*. We hypothesize that this represents an example of host-pathogen cross talk, in which the host suppresses Salmonella virulence by increasing MTA concentrations. This would represent a novel antimicrobial mechanism and is supported by our findings that MTA plasma concentrations increase during infection ([@B17]). Future studies are needed to test how host modulation of MTA helps shape the outcome of infection at systemic sites as well as in the gut. Systemically, MTA decreases inflammatory cytokines, decreases the Salmonella burden, and, as we previously reported, modestly prolongs survival ([@B17]). In the gut, MTA could result in suppression of bacterial virulence or, alternatively, could help signal to the bacteria when and where it is appropriate to turn on the expression of key factors involved in virulence.

While no previous work examined the impact of *metJ* deletion on *S*. Typhimurium virulence, two papers reported the effects of Δ*metJ* deletion and virulence in other bacterial pathogens. Bogard et al. reported that Δ*metJ* deletion suppresses Vibrio cholerae virulence *in vivo* ([@B54]). Conversely, Cubitt et al. demonstrated that Δ*metJ* deletion increased the production of quorum sensing molecules and expression of virulence genes in the potato pa