Adhesins and host serum factors drive Yop translocation by yersinia into professional phagocytes during animal infection.
Adhesins and host serum factors drive Yop translocation by yersinia into professional phagocytes during animal infection.
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DOI：
10.1371/journal.ppat.1003415
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Mecsas J
中科院分区：
文献类型：
--
作者：
Maldonado-Arocho FJ;Green C;Fisher ML;Paczosa MK;Mecsas J
耶尔森氏菌将Yops递送到多种类型的培养细胞中，但在动物感染期间主要递送到专职吞噬细胞和B细胞中。动物感染时这种细胞趋向性的基础尚不清楚。这项工作表明，有效和特异性的Yop易位到吞噬细胞的假结核耶尔森氏菌（Yptb）是一个多因素的过程，需要几个粘附素和宿主补体。当WT Yptb或多粘附素突变株ΔailΔinvΔyadA在组织中定殖至相当水平时，Δ ailΔinvΔyadA将Yops易位至显著较少的细胞中，表明这些粘附素对于易位至大量细胞中至关重要。然而，吞噬细胞仍然被选择性地靶向易位，表明其他细菌和/或宿主因素有助于这一功能。补体耗竭显示，补体限制性感染由ΔailΔinvΔyadA而非WT引起，表明粘附素通过预防调理吞噬作用或通过抑制促炎细胞因子的产生解除小鼠中的补体。此外，在三种粘附素和补体的情况下，靶向易位的细胞谱显著改变，表明耶尔森氏菌粘附素和补体在动物感染期间直接Yop易位到中性粒细胞中。总之，这些发现表明，在感染的组织中，耶尔森氏菌使用粘附素解除补体依赖性杀伤，并有效地将Yops转移到吞噬细胞中。许多细菌病原体使用针状结构将蛋白质递送到宿主细胞中以引起疾病。耶尔森氏菌使用一种称为III型分泌系统的结构，将一组6-7种蛋白质（称为Yops）递送到宿主细胞中。这些Yops的作用是拆除宿主的防御并建立感染。已经提出细菌粘附素和宿主因子促进Yops适当递送到特定哺乳动物细胞中。我们确定了三个假结核耶尔森氏菌粘附素，显着有助于细菌的生存和有效的Yop交付到宿主细胞在动物感染。我们还证明，宿主血清因子与耶尔森氏菌粘附素的组合有助于注射Yops的细胞数量和注射靶向的特定细胞类型。我们的研究表明，细菌粘附素和宿主因子有助于在感染过程中有效地将效应蛋白递送到靶向宿主细胞中。
Yersinia delivers Yops into numerous types of cultured cells, but predominantly into professional phagocytes and B cells during animal infection. The basis for this cellular tropism during animal infection is not understood. This work demonstrates that efficient and specific Yop translocation into phagocytes by Yersinia pseudotuberculosis (Yptb) is a multi-factorial process requiring several adhesins and host complement. When WT Yptb or a multiple adhesin mutant strain, ΔailΔinvΔyadA, colonized tissues to comparable levels, ΔailΔinvΔyadA translocated Yops into significantly fewer cells, demonstrating that these adhesins are critical for translocation into high numbers of cells. However, phagocytes were still selectively targeted for translocation, indicating that other bacterial and/or host factors contribute to this function. Complement depletion showed that complement-restricted infection by ΔailΔinvΔyadA but not WT, indicating that adhesins disarm complement in mice either by prevention of opsonophagocytosis or by suppressing production of pro-inflammatory cytokines. Furthermore, in the absence of the three adhesins and complement, the spectrum of cells targeted for translocation was significantly altered, indicating that Yersinia adhesins and complement direct Yop translocation into neutrophils during animal infection. In summary, these findings demonstrate that in infected tissues, Yersinia uses adhesins both to disarm complement-dependent killing and to efficiently translocate Yops into phagocytes. Many bacterial pathogens use a needle-like structure to deliver proteins into host cells to cause disease. Yersinia species use one such structure, called a type III secretion system, to deliver a set of 6–7 proteins, called Yops, into host cells. These Yops act to dismantle host defenses and establish infection. Bacterial adhesins and host factors have been suggested to promote proper delivery of Yops into specific mammalian cells. We identify three Yersinia pseudotuberculosis adhesins that significantly contribute to bacterial survival and efficient Yop delivery into host cells during animal infection. We also demonstrate that host serum factors in combination with Yersinia adhesins contribute to the number of cells that are injected with Yops and to the specific cell types targeted for injection. Our study illustrates that bacterial adhesins and host factors contribute to efficient delivery of effector proteins into targeted host cells during infection.
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影响因子：
3.1
作者：
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影响因子：
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作者：
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