ity. In contrast to this hypothesis, deleting *metJ* in wild-type and Δ*hilD* backgrounds resulted in the same decreases in motility ([Fig. 6C](#F6){ref-type="fig"}). Therefore, MTA regulation of SPI-1 is not necessary for the effects of the metabolite on motility.

These findings are consistent with MTA independently regulating the SPI-1 pathway and motility regulon. This is in line with previous observations that while SPI-1 and flagellar gene expression are often correlated, few SPI-1 regulators control invasion by modulating the activity of the flagellar regulon and FliZ ([@B46]). We hypothesize that MTA suppresses SPI-1 and motility by interacting with a currently unknown factor upstream of both pathways. Importantly, if MTA interacts with a factor upstream of these virulence pathways, then other virulence pathways may also be suppressed by MTA.

Disruption of bacterial methionine metabolism impairs virulence *in vivo*. {#sec2-7}
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Based on our findings that multiple virulence pathways are disrupted in the Δ*metJ* mutant, we hypothesized that the Δ*metJ* mutant would have impaired virulence *in vivo*. To test this, we orally coinfected C57BL/6J mice with wild-type and Δ*metJ* mutant *S*. Typhimurium and measured the bacteria\'s ability to infect and disseminate to the spleen. We found that the Δ*metJ* mutant had a 30-fold reduction in fitness compared to wild-type *S*. Typhimurium by 5 days postinfection ([Fig. 7A](#F7){ref-type="fig"}).

![*metJ* deletion suppresses *S*. Typhimurium virulence *in vivo* independently of SPI-1. (A) *metJ* deletion reduced bacterial fitness in models of oral infection. C57BL/6J mice were infected with 10^6^ total *S*. Typhimurium bacteria from a 1:1 mixture of wild-type and Δ*metJ* bacteria by oral gavage. Spleens were harvested at 5 days postinfection, and bacteria were quantified to calculate the competitive (Comp.) index. (B) *metJ* deletion reduces bacterial fitness independently of SPI-1. C57B