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首页> 外文期刊>Infection and immunity >The DnaK/DnaJ Chaperone Machinery of Salmonella enterica Serovar Typhimurium Is Essential for Invasion of Epithelial Cells and Survival within Macrophages, Leading to Systemic Infection
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The DnaK/DnaJ Chaperone Machinery of Salmonella enterica Serovar Typhimurium Is Essential for Invasion of Epithelial Cells and Survival within Macrophages, Leading to Systemic Infection

机译：鼠伤寒沙门氏菌鼠伤寒沙门氏菌的DnaK / DnaJ分子伴侣机制对于上皮细胞的侵袭和巨噬细胞的存活至关重要，从而导致系统性感染

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Salmonella enterica serovar Typhimurium, similar to various facultative intracellular pathogens, has been shown to respond to the hostile conditions inside macrophages of the host organism by inducing stress proteins, such as DnaK. DnaK forms a chaperone machinery with the cochaperones DnaJ and GrpE. To elucidate the role of the DnaK chaperone machinery in the pathogenesis of S. enterica serovar Typhimurium, we first constructed an insertional mutation in the dnaK-dnaJ operon of pathogenic strain χ3306. The DnaK/DnaJ-depleted mutant was temperature sensitive for growth, that is, nonviable above 39°C. We then isolated a spontaneously occurring revertant of the dnaK-dnaJ-disrupted mutant at 39°C and used it for infection of mice. The mutant lost the ability to cause a lethal systemic disease in mice. The impaired ability for virulence was restored when a functional copy of the dnaK-dnaJ operon was provided, suggesting that the DnaK/DnaJ chaperone machinery is required by Salmonella for the systemic infection of mice. This result also indicates that with respect to the DnaK/DnaJ chaperone machinery, the cellular requirements for growth at a high temperature are not identical to the cellular requirements for the pathogenesis of Salmonella. Macrophage survival assays revealed that the DnaK/DnaJ-depleted mutant could not survive or proliferate at all within macrophages. Of further interest are the findings that the mutant could neither invade cultured epithelial cells nor secrete any of the invasion proteins encoded within Salmonella pathogenicity island 1. This is the first time that the DnaK/DnaJ chaperone machinery has been shown to be involved in bacterial invasion of epithelial cells.
机译：与各种兼性细胞内病原体相似， Salmonella enterica 血清型鼠伤寒沙门氏菌通过诱导应激蛋白（例如DnaK）对宿主生物巨噬细胞内部的敌对条件作出反应。 DnaK与DnaJ和GrpE的陪伴分子组成了一个陪伴分子机器。阐明DnaK分子伴侣机制在 S发病机理中的作用。鼠伤寒血清型鼠伤寒沙门氏菌，我们首先在病原菌χ3306的 dnaK - dnaJ 操纵子中构建了一个插入突变。 DnaK / DnaJ耗尽的突变体对生长温度敏感，也就是说，在39°C以上不能存活。然后，我们在39°C分离出了 dnaK - dnaJ 干扰突变的自发回复体，并将其用于小鼠感染。该突变体丧失了引起小鼠致命性系统疾病的能力。提供了功能性拷贝的 dnaK - dnaJ 操纵子后，恢复了毒性能力受损，这表明 Salmonella < / em>用于小鼠的全身感染。该结果还表明，对于DnaK / DnaJ分子伴侣机制，在高温下生长的细胞需求与沙门氏菌的致病细胞需求不同。巨噬细胞生存测定表明，DnaK / DnaJ耗尽的突变体在巨噬细胞中根本无法生存或增殖。进一步有趣的发现是该突变体既不能侵入培养的上皮细胞，也不能分泌在 Salmonella 致病岛1中编码的任何入侵蛋白。这是DnaK / DnaJ分子伴侣机制首次被发现。证明与细菌侵袭上皮细胞有关。

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