Intestinal luminal polyamines support the gut colonization of enteric bacterial pathogens by modulating flagellar motility and nitrate respiration.

UNLABELLED: Salmonella enterica serovar Typhimurium (STm) is an etiological agent of common foodborne diseases and a major health concern worldwide. STm gastrointestinal infection induces intestinal inflammation, allowing STm outgrowth in the gut lumen by exploiting inflammation-induced host factors. Polyamines, including putrescine and spermidine, are crucial for both intestinal homeostasis and STm infectivity. However, our understanding of polyamines' role in STm infection remains incomplete. This study aimed to elucidate that role. We found that defects in polyamine uptake‒dependent homeostasis altered the expression profiles of genes involved in STm flagellar motility and nitrate respiration. Spermidine supplementation restored the expression of the nar and nap operons, which encode distinct nitrate reductases, in an STm mutant with impaired polyamine homeostasis. Thus, the polyamine homeostasis-defective STm mutant exhibited reduced nitrate respiration, which spermidine supplementation rescued. In contrast, both putrescine and spermidine partially reversed the impaired expression of flagellin in this mutant. Additionally, the mutant exhibited a higher proportion of nonmotile cells compared with the wild-type strain. Finally, we demonstrated that the reduced gut colonization of this mutant was due to decreased nitrate respiration and flagellar motility. Moreover, polyamine supplementation enhanced the luminal growth of STm and a pathobiont, Escherichia coli. Our findings reveal that intestinal luminal polyamines support the growth of enteric bacterial pathogens in the intestinal tract.

IMPORTANCE: Microbiota-derived metabolites play crucial roles in gastrointestinal infections caused by enteric pathogens. One notable example is short-chain fatty acids, such as acetate, propionate, and butyrate, which are beneficial for health and protective against infection. This study highlights that the gut microbiota‒derived polyamine spermidine drives luminal growth of enteric bacterial pathogens. The findings suggest that higher luminal levels of polyamines may be a risk factor for enteric infections. Therefore, regulating luminal polyamines could represent a promising therapeutic intervention for gastrointestinal infections.