Miki Tsuyoshi, Kurihara Shin, Uemura Takeshi, Ami Yuta, Ito Masahiro, Haneda Takeshi, Furuchi Takemitsu, Okada Nobuhiko, Minamino Tohru, Kim Yun-Gi
Department of Microbiology, School of Pharmacy, Kitasato University, Tokyo, Japan.
Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama, Japan.
mBio. 2025 Sep 10;16(9):e0178625. doi: 10.1128/mbio.01786-25. Epub 2025 Aug 11.
serovar Typhimurium (Tm) is an etiological agent of common foodborne diseases and a major health concern worldwide. Tm gastrointestinal infection induces intestinal inflammation, allowing Tm outgrowth in the gut lumen by exploiting inflammation-induced host factors. Polyamines, including putrescine and spermidine, are crucial for both intestinal homeostasis and Tm infectivity. However, our understanding of polyamines' role in Tm 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 Tm flagellar motility and nitrate respiration. Spermidine supplementation restored the expression of the and operons, which encode distinct nitrate reductases, in an Tm mutant with impaired polyamine homeostasis. Thus, the polyamine homeostasis-defective Tm 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 Tm and a pathobiont, . Our findings reveal that intestinal luminal polyamines support the growth of enteric bacterial pathogens in the intestinal tract.
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.
鼠伤寒血清型（Tm）是常见食源性疾病的病原体，也是全球主要的健康问题。Tm胃肠道感染会引发肠道炎症，通过利用炎症诱导的宿主因子使Tm在肠腔中大量繁殖。包括腐胺和亚精胺在内的多胺对于肠道稳态和Tm的感染性都至关重要。然而，我们对多胺在Tm感染中作用的理解仍不完整。本研究旨在阐明这一作用。我们发现，依赖多胺摄取的稳态缺陷改变了参与Tm鞭毛运动和硝酸盐呼吸的基因表达谱。在多胺稳态受损的Tm突变体中，补充亚精胺可恢复编码不同硝酸盐还原酶的 和 操纵子的表达。因此，多胺稳态缺陷的Tm突变体表现出硝酸盐呼吸减少，补充亚精胺可挽救这一现象。相比之下，腐胺和亚精胺都能部分逆转该突变体中鞭毛蛋白表达的受损情况。此外，与野生型菌株相比，该突变体中不运动细胞的比例更高。最后，我们证明该突变体在肠道中的定殖减少是由于硝酸盐呼吸和鞭毛运动降低所致。此外，补充多胺可增强Tm和一种共生菌在肠腔中的生长。我们的研究结果表明，肠道腔中的多胺支持肠道细菌病原体在肠道中的生长。
微生物群衍生的代谢产物在肠道病原体引起的胃肠道感染中起关键作用。一个显著的例子是短链脂肪酸，如乙酸盐、丙酸盐和丁酸盐，它们对健康有益且具有抗感染作用。本研究强调，肠道微生物群衍生的多胺亚精胺可促进肠道细菌病原体在肠腔中的生长。研究结果表明，肠腔中多胺水平升高可能是肠道感染的一个危险因素。因此，调节肠腔中的多胺可能是胃肠道感染的一种有前景的治疗干预措施。
