Aranjuez George F, Patel Om, Patel Dev, Jewett Travis J
Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
Microbiol Spectr. 2025 Apr;13(4):e0259624. doi: 10.1128/spectrum.02596-24. Epub 2025 Mar 10.
() is an obligate, intracellular Gram-negative bacteria and the leading bacterial sexually transmitted infection in the United States. manipulates the host cell biology using various secreted bacterial effectors during its intracellular development. The early effector ranslocated ctin-ecruiting hosphoprotein (Tarp), important for entry, has a well-characterized C-terminal region which can polymerize and bundle F-actin. In contrast, not much is known about the function of the N-terminus of Tarp (N-Tarp), though present in many spp. To address this, we use as an cell biology platform to study N-Tarp-host interactions. Transgenic expression of N-Tarp in results in developmental phenotypes consistent with altered host Salvador-Warts-Hippo signaling, a conserved signaling cascade that regulates host cell proliferation and survival. We studied the N-Tarp function in larval imaginal wing discs, which are sensitive to perturbations in Hippo signaling. N-Tarp causes wing disc overgrowth and a concomitant increase in adult wing size, phenocopying overexpression of the Hippo co-activator Yorkie. N-Tarp also causes upregulation of Hippo target genes. Last, N-Tarp-induced phenotypes can be rescued by reducing the levels of Yorkie or the Hippo target genes and . Thus, we provide evidence that the N-terminal region of the effector Tarp is sufficient to alter host Hippo signaling and acts upstream of the co-activator Yorkie.
The survival of obligate intracellular bacteria like depends on the survival of the host cell itself. It is not surprising that -infected cells are resistant to cell death, though the exact molecular mechanism is largely unknown. Here, we establish that the N-terminal region of the well-known early effector Tarp can alter Hippo signaling in vivo. Only recently implicated in infection, the Hippo pathway is known to promote cell survival. Our findings illuminate one possible mechanism for to promote host cell survival during infection. We further demonstrate the utility of as a tool in the study of effector function.
（病原体名称）是一种专性细胞内革兰氏阴性菌，是美国主要的细菌性性传播感染病原体。（病原体名称）在其细胞内发育过程中，利用各种分泌的细菌效应蛋白来操控宿主细胞生物学特性。早期效应蛋白转位肌动蛋白募集磷酸化蛋白（Tarp）对（病原体名称）进入宿主细胞很重要，其C端区域特征明确，能够使F - 肌动蛋白聚合和束集。相比之下，尽管Tarp的N端（N - Tarp）存在于许多（病原体名称）菌株中，但对其功能了解甚少。为了解决这个问题，我们将（病原体名称）用作细胞生物学平台来研究N - Tarp与宿主的相互作用。在（宿主细胞名称）中N - Tarp的转基因表达导致发育表型改变，这与宿主萨尔瓦多 - 沃茨 - 河马信号通路（Salvador - Warts - Hippo signaling）改变一致，该信号级联保守，调节宿主细胞增殖和存活。我们在对河马信号通路扰动敏感的幼虫成虫翅芽中研究了N - Tarp的功能。N - Tarp导致翅芽过度生长，并伴随成虫翅膀尺寸增大，模拟了河马共激活因子Yorkie的过表达。N - Tarp还导致河马靶基因上调。最后，通过降低Yorkie或河马靶基因（基因名称1）和（基因名称2）的水平，可以挽救N - Tarp诱导的表型。因此，我们提供了证据表明（病原体名称）效应蛋白Tarp的N端区域足以改变宿主河马信号通路，并在共激活因子Yorkie的上游起作用。
像（病原体名称）这样的专性细胞内细菌的存活取决于宿主细胞本身的存活。虽然确切的分子机制很大程度上未知，但受（病原体名称）感染的细胞对细胞死亡具有抗性并不奇怪。在这里，我们确定了著名的（病原体名称）早期效应蛋白Tarp的N端区域可以在体内改变河马信号通路。河马信号通路直到最近才与（病原体名称）感染相关联，已知其促进细胞存活。我们的发现揭示了（病原体名称）在感染期间促进宿主细胞存活的一种可能机制。我们进一步证明了（宿主细胞名称）作为研究效应蛋白功能工具的实用性。
