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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella
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Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella

机译：效应蛋白对Rab29的蛋白水解靶向可区分人类适应的沙门氏菌和宽宿主沙门氏菌的细胞内区室

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摘要

Unlike broad-host Salmonella serovars, which cause self-limiting disease. Salmonella enterica serovar Typhi can infect only humans causing typhoid fever, a life-threatening systemic disease. The molecular bases for these differences are presently unknown. Here we show that the GTPase Rab29 (Rab7L1) distinguishes the intracellular vacu-ole of human-adapted and broad-host Salmonella serovars. A screen to identify host factors required for the export of typhoid toxin, which is exclusively encoded by the human-specific Salmonella enterica serovars Typhi (5. Typhi) and Paratyphi (S. Paratyphi) identified Rab29. We found that Rab29 is recruited to the 5. Typhi-containing vacuole but not to vacuoles containing broad-host Salmonella. We observed that in cells infected with broad-host Salmonella Rab29 is specifically cleaved by the proteolytic activity of GtgE, a unique type III secretion effector protein that is absent from S. Typhi. An 5. Typhi strain engineered to express GtgE and therefore able to cleave Rab29 exhibited increased intracellular replication in human macrophages. These findings indicate significant differences in the intracellular biology of human-adapted and broad-host Salmonella and show how subtle differences in the assortment of effector proteins encoded by highly related pathogens can have a major impact in their biology.
机译：不像宽宿主沙门氏菌，它们会引起自限性疾病。肠炎沙门氏菌伤寒沙门氏菌只能感染导致伤寒的致命人类，这种伤寒是一种致命的全身性疾病。目前尚不清楚这些差异的分子基础。在这里，我们显示GTPase Rab29（Rab7L1）区分了人类适应和宽宿主沙门氏菌血清的胞内真空。鉴定出伤寒毒素出口所需的宿主因子的屏幕，由人特异性肠炎沙门氏菌鼠伤寒沙门氏菌（5. Typhi）和副伤寒沙门氏菌（S. Paratyphi）专门编码，鉴定出Rab29。我们发现Rab29被募集到5. Typhi含液泡，但不募集到含有宽宿主沙门氏菌的液泡。我们观察到，在感染了广泛宿主沙门氏菌的细胞中，沙门氏菌Rab29被GtgE（一种独特的III型分泌效应蛋白，S。Typhi不存在）的蛋白水解活性特异切割。工程表达GtgE并因此能够裂解Rab29的5. Typhi菌株在人类巨噬细胞中显示出增加的细胞内复制。这些发现表明，人类适应和广泛宿主沙门氏菌的细胞内生物学存在显着差异，并表明高度相关病原体编码的效应蛋白种类的细微差异如何对其生物学产生重大影响。

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