Twin-Arginine Translocation System Is Involved in Citrobacter rodentium Fitness in the Intestinal Tract
Twin-Arginine Translocation System Is Involved in Citrobacter rodentium Fitness in the Intestinal Tract
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DOI：
10.1128/iai.00892-19
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发表时间：
2019-12
影响因子：
3.1
通讯作者：
Tsuyoshi Otake;Mayuka Fujimoto;Y. Hoshino;Tomomi Ishihara;Takeshi Haneda;N. Okada;T. Miki
中科院分区：
文献类型：
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作者：
Tsuyoshi Otake;Mayuka Fujimoto;Y. Hoshino;Tomomi Ishihara;Takeshi Haneda;N. Okada;T. Miki
双精氨酸易位（达特）系统不仅参与多种细胞过程，而且参与许多细菌病原体的致病过程，因此，该系统有望成为治疗感染的新靶点。据我们所知，达特系统参与由啮齿类柠檬酸杆菌引起的肠道感染尚未报道。本文研究了达特在C.啮齿类肠道感染，类似于人感染肠出血性大肠杆菌（EHEC）和肠致病性大肠杆菌。coli（EPEC）。摘要双精氨酸易位（达特）系统不仅参与了多种细胞过程，而且还参与了许多细菌病原体的致病过程，因此，该系统有望成为治疗感染的新靶点。据我们所知，达特系统参与由啮齿类柠檬酸杆菌引起的肠道感染尚未报道。本文研究了达特在C.啮齿类肠道感染，类似于人感染肠出血性大肠杆菌（EHEC）和肠致病性大肠杆菌。coli（EPEC）。梭啮齿动物达特功能丧失突变体显示出延长的肠道定植，这可以通过减少的炎症反应，特别是中性粒细胞浸润来解释。此外，达特突变体在与野生型C.啮齿动物。达特突变体也变得对胆汁酸过敏，粪便胆汁酸的增加培养了C。啮齿动物从肠腔中的清除率。最后，我们证明了C.由Tat依赖性细胞分裂缺陷诱导的啮齿动物细胞表现出对胆汁酸的抗性受损。我们的研究结果表明，达特系统参与了肠道定植的C。啮齿类，这与中性粒细胞浸润和胆汁酸抗性有关。因此，针对达特系统以及管腔胆汁酸的干预可能是治疗人类EHEC和EPEC感染的有希望的治疗策略。
The twin-arginine translocation (Tat) system is involved in not only a wide array of cellular processes but also pathogenesis in many bacterial pathogens; thus, this system is expected to become a novel therapeutic target to treat infections. To the best of our knowledge, involvement of the Tat system has not been reported in the gut infection caused by Citrobacter rodentium. Here, we studied the role of Tat in C. rodentium gut infection, which resembles human infection with enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). ABSTRACT The twin-arginine translocation (Tat) system is involved in not only a wide array of cellular processes but also pathogenesis in many bacterial pathogens; thus, this system is expected to become a novel therapeutic target to treat infections. To the best of our knowledge, involvement of the Tat system has not been reported in the gut infection caused by Citrobacter rodentium. Here, we studied the role of Tat in C. rodentium gut infection, which resembles human infection with enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). A C. rodentium Tat loss-of-function mutant displayed prolonged gut colonization, which was explained by reduced inflammatory responses and, particularly, neutrophil infiltration. Further, the Tat mutant had colonization defects upon coinfection with the wild-type strain of C. rodentium. The Tat mutant also became hypersensitive to bile acids, and an increase in fecal bile acids fostered C. rodentium clearance from the gut lumen. Finally, we show that the chain form of C. rodentium cells, induced by a Tat-dependent cell division defect, exhibits impaired resistance to bile acids. Our findings indicate that the Tat system is involved in gut colonization by C. rodentium, which is associated with neutrophil infiltration and resistance to bile acids. Interventions that target the Tat system, as well as luminal bile acids, might thus be promising therapeutic strategies to treat human EHEC and EPEC infections.