Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8022, USA.
Cell Microbiol. 2011 Jan;13(1):47-61. doi: 10.1111/j.1462-5822.2010.01516.x. Epub 2010 Aug 27.
Anaplasma phagocytophilum causes human granulocytic anaplasmosis, one of the most common tick-borne diseases in North America. This unusual obligate intracellular pathogen selectively persists within polymorphonuclear leucocytes. In this study, using the yeast surrogate model we identified an A. phagocytophilum virulence protein, AptA (A. phagocytophilum toxin A), that activates mammalian Erk1/2 mitogen-activated protein kinase. This activation is important for A. phagocytophilum survival within human neutrophils. AptA interacts with the intermediate filament protein vimentin, which is essential for A. phagocytophilum-induced Erk1/2 activation and infection. A. phagocytophilum infection reorganizes vimentin around the bacterial inclusion, thereby contributing to intracellular survival. These observations reveal a major role for the bacterial protein, AptA, and the host protein, vimentin, in the activation of Erk1/2 during A. phagocytophilum infection.
嗜吞噬细胞无形体导致人类粒细胞无形体病，这是北美的一种最常见的蜱传疾病。这种不寻常的专性细胞内病原体选择性地在多形核白细胞内持续存在。在这项研究中，我们使用酵母替代模型鉴定出一种嗜吞噬细胞无形体毒力蛋白 AptA（嗜吞噬细胞无形体毒素 A），它能激活哺乳动物 Erk1/2 丝裂原活化蛋白激酶。这种激活对于嗜吞噬细胞无形体在人类中性粒细胞内的存活很重要。AptA 与中间丝蛋白波形蛋白相互作用，这对于嗜吞噬细胞无形体诱导的 Erk1/2 激活和感染是必需的。嗜吞噬细胞无形体感染将波形蛋白重组到细菌包含体周围，从而有助于细胞内存活。这些观察结果揭示了细菌蛋白 AptA 和宿主蛋白波形蛋白在嗜吞噬细胞无形体感染期间激活 Erk1/2 中的主要作用。
