Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks
Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks
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DOI：
10.1172/jci39401
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发表时间：
2009-12-01
影响因子：
15.9
通讯作者：
Radolf, Justin D.
中科院分区：
文献类型：
--
作者：
Dunham-Ems, Star M.;Caimano, Melissa J.;Radolf, Justin D.
莱姆病是由病毒的传播引起的。伯氏疏螺旋体从壁虱到人类。虽然关于伯氏杆菌复制已知很多，但它在硬体内传播的途径和机制仍不清楚。为了更好地理解这一过程，我们成像了具有感染性的活体伯氏杆菌表达稳定整合的、结构性表达的GFP报告基因。利用分离的壁虱中肠和唾液腺，我们观察到伯氏伯氏杆菌通过一种我们认为是一种新的双相传播模式通过喂食的壁虱进行传播。在第一阶段，复制的螺旋体在摄食开始时位于整个中肠的不同深度，形成由不活动的生物体组成的网络，这些网络向上皮的基底外侧表面推进，同时附着于分化、肥大和分离的上皮细胞。在传播的第二阶段，不活动的螺旋体转变为活动的有机体，穿过基底膜进入血腔，然后迁移到唾液腺。我们将传播的第一阶段命名为“黏附介导的迁移”，并提供证据表明，它涉及到由喂食的扁虱中肠阐述的一个或多个扩散因子对螺旋体运动的抑制。我们的研究首次将螺旋体的传播动力学与中肠和唾液腺在充血过程中经历的复杂的形态和发育变化联系起来，挑战了传统观点，即导致莱姆病的螺旋体在硬蜱中的传播完全是由运动驱动的。
Lyme disease is caused by transmission of the. spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. in the second phase of dissemination, the non-motile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.