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OspC-Independent Infection and Dissemination by Host-Adapted Borrelia burgdorferi

机译:宿主适应性疏螺旋体伯氏疏螺旋体的OspC独立感染和传播

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Borrelia burgdorferi OspC is required for the spirochete to establish infection in a mammal by tick transmission or needle inoculation. After a brief essential period, the protein no longer is required and the gene can be shut off. Using a system in which spirochetes contain only an unstable wild-type copy of the ospC gene, we can obtain mice persistently infected with bacteria lacking OspC. We implanted pieces of infected mouse skin subcutaneously in na?ve mice, using donors carrying wild-type or ospC mutant spirochetes, and found that both could infect mice by this method, with similar numbers of wild-type or ospC mutant spirochetes disseminated throughout the tissues of recipient mice. Recipient mouse immune responses to tissue transfer-mediated infection with wild-type or ospC mutant spirochetes were similar. These experiments demonstrate that mammalian host-adapted spirochetes can infect and disseminate in mice in the absence of OspC, thereby circumventing this hallmark of tick-derived or in vitro-grown spirochetes. We propose a model in which OspC is one of a succession of functionally equivalent, essential proteins that are synthesized at different stages of mammalian infection. In this model, another protein uniquely present on host-adapted spirochetes performs the same essential function initially fulfilled by OspC. The strict temporal control of B. burgdorferi outer surface protein gene expression may reflect immunological constraints rather than distinct functions.
机译: Borrelia burgdorferi 螺旋体需要通过OspC才能通过壁虱传播或针头接种在哺乳动物中建立感染。经过短暂的必要时间后,不再需要该蛋白质,并且可以关闭该基因。使用其中螺旋体仅包含 ospC 基因的不稳定野生型拷贝的系统,我们可以获得持续感染缺乏OspC细菌的小鼠。我们使用携带野生型或 ospC 突变螺旋体的供体将皮下感染的小鼠皮肤皮下植入幼稚的小鼠体内,发现它们都可以通过这种方法感染小鼠,且野生型数量相似或 ospC 突变体螺旋体散布到受体小鼠的整个组织中。收件人小鼠对野生型或 ospC 突变螺旋体的组织转移介导的感染的免疫反应相似。这些实验表明,在没有OspC的情况下,适应哺乳动物宿主的螺旋体可以在小鼠中感染和传播,从而规避了tick衍生或体外生长的螺旋体的标志。我们提出一种模型,其中OspC是在哺乳动物感染的不同阶段合成的一系列功能等效的必需蛋白之一。在该模型中,宿主适​​应螺旋体上独特存在的另一种蛋白质执行了OspC最初实现的相同基本功能。 B的严格时间控制。 burgdorferi外表面蛋白基因的表达可能反映了免疫学上的限制而不是独特的功能。

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