Secretome analysis defines the major role of SecDF in Staphylococcus aureus virulence.

Secretome analysis defines the major role of SecDF in Staphylococcus aureus virulence.
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DOI:
10.1371/journal.pone.0063513
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Senn MM
Senn MM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Quiblier C;Seidl K;Roschitzki B;Zinkernagel AS;Berger-Bächi B;Senn MM

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Sec通路在蛋白质输出和膜插入中起着重要作用,包括主要细菌毒力决定因素的分泌。辅助成分SecDF被认为有助于蛋白质的输出。金黄色葡萄球菌secDF的缺失已被证明可以降低耐药性,改变细胞分离,并改变某些毒力因子的表达。为了分析金黄色葡萄球菌中secDF缺失对蛋白质分泌的影响,进行了定量分泌组分析。在secDF突变体的上清液中发现许多含有Sec信号的毒力相关蛋白减少。然而,与野生型相比,两种依赖secDF的水解酶增加,这表明在secDF缺失时发生了额外的间接调节作用。secDF突变体在人脐静脉内皮细胞中的粘附性、侵袭性和细胞毒性均降低。毒力显著降低使用花廊虫模型。总之,SecDF是控制金黄色葡萄球菌感染的一个有希望的治疗靶点。
The Sec pathway plays a prominent role in protein export and membrane insertion, including the secretion of major bacterial virulence determinants. The accessory Sec constituent SecDF has been proposed to contribute to protein export. Deletion of Staphylococcus aureus secDF has previously been shown to reduce resistance, to alter cell separation, and to change the expression of certain virulence factors. To analyse the impact of the secDF deletion in S. aureus on protein secretion, a quantitative secretome analysis was performed. Numerous Sec signal containing proteins involved in virulence were found to be decreased in the supernatant of the secDF mutant. However, two Sec-dependent hydrolases were increased in comparison to the wild type, suggesting additional indirect, regulatory effects to occur upon deletion of secDF. Adhesion, invasion, and cytotoxicity of the secDF mutant were reduced in human umbilical vein endothelial cells. Virulence was significantly reduced using a Galleria mellonella insect model. Altogether, SecDF is a promising therapeutic target for controlling S. aureus infections.
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