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Nature:科学家发现抵御肠道感染的关键途径

来源:生物谷 2013-09-13 00:01

2013年9月12日 讯 /生物谷BIOON/ --近日,来自墨尔本皇家儿童医院等处的研究者通过研究发现,致命大肠杆菌可以阻断一种机体保护肠道免于此菌感染的途径,这种致命大肠杆菌引发的感染通常在幼儿中尤其严重,而且会引发腹泻以及其它比如肾脏损伤等并发症,相关研究成果刊登于国际著名杂志Nature上。

机体保护肠道免于感染的这种途径在此前并不知道,但是该途径缺失却和炎性肠病直接相关;这项研究为科学家们理解该途径缺失所引发的病症以及其发生的分子机制提供了思路。研究者Elizabeth Hartland说道,本文研究为我们提供了一个例子,这样我们就能够分析致命大肠杆菌在机体中开关这条关键路径的分子机制,从而为我们抵御细菌感染保护正常的肠道功能提供一定帮助。

运用基本的知识研究者就可以进行深入研究,来开发改善炎性肠病患者的疗法,这种引发腹泻的细菌可以使用一种针状样的结构来将毒素注射入肠粘膜细胞中,从而阻碍细胞死亡,这就可以使得细菌可以在肠道中生存以及扩散,进而引发一系列疾病。

被注射的毒素可以麻痹感染的细胞,阻断其和免疫细胞之间的通讯,这样免疫细胞就不能够感知并且消除机体中有危害的致病菌。痢疾感染是发展中国家影响人们健康的一个主要原因,而引发痢疾的主要致病菌就是致命大肠杆菌,当然该细菌的感染也常在发达国家比如澳大利亚发生。(生物谷Bioon.com)

A type III effector antagonizes death receptor signalling during bacterial gut infection

Jaclyn S. Pearson Cristina Giogha Sze Ying Ong Catherine L. Kennedy Michelle Kelly Keith S. Robinson Tania Wong Fok Lung Ashley Mansell Patrice Riedmaier Clare V. L. Oates Ali Zaid Sabrina Mühlen Valerie F. Crepin Olivier Marches Ching-Seng Ang Nicholas A. Williamson Lorraine A. O’Reilly Aleksandra Bankovacki Ueli Nachbur Giuseppe Infusini Andrew I. Webb John Silke Andreas Strasser Gad Frankel Elizabeth L. Hartland

Successful infection by enteric bacterial pathogens depends on the ability of the bacteria to colonize the gut, replicate in host tissues and disseminate to other hosts. Pathogens such as Salmonella, Shigella and enteropathogenic and enterohaemorrhagic (EPEC and EHEC, respectively) Escherichia coli use a type III secretion system (T3SS) to deliver virulence effector proteins into host cells during infection that promote colonization and interfere with antimicrobial host responses1, 2, 3. Here we report that the T3SS effector NleB1 from EPEC binds to host cell death-domain-containing proteins and thereby inhibits death receptor signalling. Protein interaction studies identified FADD, TRADD and RIPK1 as binding partners of NleB1. NleB1 expressed ectopically or injected by the bacterial T3SS prevented Fas ligand or TNF-induced formation of the canonical death-inducing signalling complex (DISC) and proteolytic activation of caspase-8, an essential step in death-receptor-induced apoptosis. This inhibition depended on the N-acetylglucosamine transferase activity of NleB1, which specifically modified Arg 117 in the death domain of FADD. The importance of the death receptor apoptotic pathway to host defence was demonstrated using mice deficient in the FAS signalling pathway, which showed delayed clearance of the EPEC-like mouse pathogen Citrobacter rodentium and reversion to virulence of an nleB mutant. The activity of NleB suggests that EPEC and other attaching and effacing pathogens antagonize death-receptor-induced apoptosis of infected cells, thereby blocking a major antimicrobial host response.

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