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

by Tsuyoshi Miki, Takeshi Uemura, Miki Kinoshita, Yuta Ami, Masahiro Ito, Nobuhiko Okada, Takemitsu Furuchi, Shin Kurihara, Takeshi Haneda, Tohru Minamino, Yun-Gi Kim

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 (STm) exploits host polyamines for the functional expression of virulence factors. An STm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of STm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. STm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated STm colonization, whereas polyamine supplementation augmented STm pathogenesis. Our work reveals that host polyamines are a key factor promoting STm infection, and therefore a promising therapeutic target for bacterial infection.