Salmonella Typhimurium exploits host polyamines for assembly of the type 3 secretion machinery

Bacterial pathogens utilize the factors of their hosts to infect them, but which factors they exploit remain poorly defined. Here, we show that a pathogenic Salmonella enterica serovar Typhimurium ( S Tm) exploits host polyamines for the functional expression of virulence factors. An S Tm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of S Tm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. S Tm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated S Tm colonization, whereas polyamine supplementation augmented S Tm pathogenesis. Our work reveals that host polyamines are a key factor promoting S Tm infection, and therefore a promising therapeutic target for bacterial infection.