A novel secretion pathway of Salmonella enterica acts as an antivirulence modulator during salmonellosis.
A novel secretion pathway of Salmonella enterica acts as an antivirulence modulator during salmonellosis.
复制标题
DOI：
10.1371/journal.ppat.1000036
复制
发表时间：
2008-04-04
期刊：
影响因子：
6.7
通讯作者：
Finlay BB
中科院分区：
文献类型：
--
作者：
Gal-Mor O;Gibson DL;Baluta D;Vallance BA;Finlay BB
沙门氏菌是革兰氏阴性肠道致病菌，感染多种脊椎动物宿主。像任何其他生物体一样，蛋白质分泌是沙门氏菌生物学各个方面必不可少的基本过程。在这里，我们报告的鉴定和表征的水平收购，自主和以前未报告的分泌途径。在鼠伤寒沙门氏菌中，这种新的分泌途径由STM 1669和STM 1668编码，分别命名为STM 166 T和STM 166 S。我们发现，ZirT是本地化的细菌外膜，预计将采取一个紧凑的β-桶构象，并作为一个转运ZirS的功能。ZirS是一种胞外蛋白，其以ZirT依赖的方式分泌到细胞外环境中。发现ZirTS分泌途径与双伴侣分泌（TPS）系统和粘附的内膜/侵袭素家族成员共享几个重要特征。我们发现，锌的影响，并在体内，诱导的recruitt发生独特的沙门氏菌定植在小肠，但不是在系统性网站。此外，在小鼠的急性和持续感染期间，在粪便颗粒中脱落的沙门氏菌中发生了BMPT的强表达。ZirTS的灭活导致沙门氏菌在小鼠口腔感染期间的高毒力表型。累积起来，这些结果表明，ZirTS途径发挥独特的作用，在全身性疾病的抗病力调节剂，并参与微调沙门氏菌病的宿主-病原体平衡。沙门氏菌属细菌是重要的人类病原体，也是食源性疾病的主要原因。与所有其他生物体一样，蛋白质分泌是一个基本过程，这是沙门氏菌生物学许多不同方面所需的，包括细胞器的生物发生，营养物质的获取和毒力。在这项工作中，我们描述了沙门氏菌中一种新的分泌途径，称为ZirTS。该途径由一个输出蛋白（ZirS）和一个指定的膜转运蛋白（ZirT）组成，后者介导ZirS分泌到细胞外环境。使用沙门氏菌感染的小鼠模型，我们发现ZirTS系统在沙门氏菌定植于小肠和沙门氏菌在急性和持续感染期间在粪便颗粒中脱落中被诱导。有趣的是，ZirTS的失活导致沙门氏菌在小鼠口腔感染期间的高毒力表型。这些观察结果表明，ZirTS途径作为抗病力调节剂发挥着独特的作用，并参与疾病期间微调宿主-病原体相互作用。我们的研究阐明了发病机制中的一个新兴主题，强调病原体限制其对感染细胞的影响以实现与宿主的平衡的重要性。
Salmonella spp. are Gram-negative enteropathogenic bacteria that infect a variety of vertebrate hosts. Like any other living organism, protein secretion is a fundamental process essential for various aspects of Salmonella biology. Herein we report the identification and characterization of a horizontally acquired, autonomous and previously unreported secretion pathway. In Salmonella enterica serovar Typhimurium, this novel secretion pathway is encoded by STM1669 and STM1668, designated zirT and zirS, respectively. We show that ZirT is localized to the bacterial outer membrane, expected to adopt a compact β-barrel conformation, and functions as a translocator for ZirS. ZirS is an exoprotein, which is secreted into the extracellular environment in a ZirT-dependent manner. The ZirTS secretion pathway was found to share several important features with two-partner secretion (TPS) systems and members of the intimin/invasin family of adhesions. We show that zirTS expression is affected by zinc; and that in vivo, induction of zirT occurs distinctively in Salmonella colonizing the small intestine, but not in systemic sites. Additionally, strong expression of zirT takes place in Salmonella shed in fecal pellets during acute and persistent infections of mice. Inactivation of ZirTS results in a hypervirulence phenotype of Salmonella during oral infection of mice. Cumulatively, these results indicate that the ZirTS pathway plays a unique role as an antivirulence modulator during systemic disease and is involved in fine-tuning a host–pathogen balance during salmonellosis. Bacteria of the Salmonella genus are important human pathogens and a leading cause of food-borne illness. Like for all other living organisms, protein secretion is a fundamental process, which is required for many different aspects of Salmonella biology including biogenesis of organelles, nutrient acquisition, and virulence. In this work we describe a new secretion pathway in Salmonella termed ZirTS. This pathway consists of an exported protein (ZirS) and a designated membrane translocator (ZirT), which mediates the secretion of ZirS to the extracellular milieu. Using a mouse model of Salmonella infection, we found that the ZirTS system is induced in Salmonella colonizing the small intestine and in Salmonella shed in fecal pellets during acute and persistent infections. Interestingly, inactivation of ZirTS results in a hypervirulence phenotype of Salmonella during oral infection of mice. These observations indicate that the ZirTS pathway plays a unique role as an antivirulence modulator and is involved in fine-tuning host–pathogen interactions during disease. Our study elucidates an emerging theme in pathogenesis emphasizing the importance of pathogens to limit their effects upon the cells they infect in order to achieve a balance with their host.
登录
查看更多内容
影响因子：
15.9
作者：
Baumler, AJ
通讯作者：
Baumler, AJ
DOI：
10.1073/pnas.0505401102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Coombes, BK;Wickham, ME;Finlay, BB
通讯作者：
Finlay, BB
影响因子：
5.8
作者：
Gal-Mor, Ohad;Valdez, Yanet;Finlay, B. Brett
通讯作者：
Finlay, B. Brett
DOI：
10.1073/pnas.0400291101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Clantin, B;Hodak, H;Villeret, V
通讯作者：
Villeret, V
DOI：
10.1111/j.1432-1033.1983.tb07594.x
发表时间：
1983-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
FREUDL, R;COLE, ST
通讯作者：
COLE, ST