SadA, a Trimeric Autotransporter from Salmonella enterica Serovar Typhimurium, Can Promote Biofilm Formation and Provides Limited Protection against Infection

SadA, a Trimeric Autotransporter from Salmonella enterica Serovar Typhimurium, Can Promote Biofilm Formation and Provides Limited Protection against Infection
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DOI:
10.1128/iai.05592-11
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发表时间:
2011-11-01
影响因子:
3.1
通讯作者:
Henderson, Ian R.
Henderson, Ian R.
中科院分区:
医学2区
文献类型:
--
作者:
Raghunathan, Dhaarini;Wells, Timothy J.;Henderson, Ian R.

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肠道沙门氏菌是世界范围内发病率和撒哈拉以南非洲儿童和免疫功能低下个体死亡率的主要原因。沙门氏菌的外膜蛋白具有重要意义,因为它们位于病原体和宿主之间的界面,它们可以有助于粘附、定殖和毒力,并且它们经常是抗体介导的免疫的靶标。在这项研究中,SadA,一个所谓的三聚体的自转运粘附沙门氏菌血清型鼠伤寒沙门氏菌的性质进行了检查。我们证明,SadA暴露在沙门氏菌细胞表面在体外和体内感染小鼠期间。SadA的表达导致细胞聚集、生物膜形成和对人肠Caco-2上皮细胞的粘附增加。用折叠的、全长的、纯化的SadA免疫小鼠引起IgG应答,其提供针对细菌挑战的有限保护。当抗SadA IgG滴度通过施用明矾沉淀的蛋白质增强时,提供适度的额外保护。因此,尽管SadA具有多效性功能,但它不是抗体介导的针对沙门氏菌的保护的优势保护性抗原。
Salmonella enterica is a major cause of morbidity worldwide and mortality in children and immunocompromised individuals in sub-Saharan Africa. Outer membrane proteins of Salmonella are of significance because they are at the interface between the pathogen and the host, they can contribute to adherence, colonization, and virulence, and they are frequently targets of antibody-mediated immunity. In this study, the properties of SadA, a purported trimeric autotransporter adhesin of Salmonella enterica serovar Typhimurium, were examined. We demonstrated that SadA is exposed on the Salmonella cell surface in vitro and in vivo during infection of mice. Expression of SadA resulted in cell aggregation, biofilm formation, and increased adhesion to human intestinal Caco-2 epithelial cells. Immunization of mice with folded, full-length, purified SadA elicited an IgG response which provided limited protection against bacterial challenge. When anti-SadA IgG titers were enhanced by administering alum-precipitated protein, a modest additional protection was afforded. Therefore, despite SadA having pleiotropic functions, it is not a dominant, protective antigen for antibody-mediated protection against Salmonella.