OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands
OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands
复制标题
DOI：
10.1172/jci200419894
复制
发表时间：
2004-01-01
影响因子：
15.9
通讯作者：
Fikrig, E
中科院分区：
文献类型：
--
作者：
Pal, U;Yang, XF;Fikrig, E
外表面蛋白C（OspC）是伯氏疏螺旋体的差异表达的主要表面脂蛋白。当螺旋体离开肩突硬蜱肠道、迁移到唾液腺并离开节肢动物载体时，ospC迅速上调。在这里，我们表明，OspC强烈结合蜱唾液腺，这表明OspC的螺旋体粘附到这个组织中的作用。使用莱姆疏螺旋体病小鼠模型的体内研究显示，虽然OspC F（ab）2片段不影响螺旋体的活力或ospC基因表达，但它们确实干扰B。蜱唾液腺的伯氏侵袭。然后，我们在B的感染性克隆中产生ospC敲除螺旋体。burgdorferi和检查他们的载体。OspC缺陷型或野生型螺旋体在未进食蜱的肠道内同样持续存在，并在蜱充血期间繁殖;然而，与野生型B不同。burgdorferi，突变体无法侵入唾液腺。唾液腺定植的OspC缺陷的螺旋体完全恢复时，这种突变体是互补的反式与携带野生型ospC基因的质粒。这些研究最终证明了OspC在B侵袭蜱唾液腺中的重要性。burgdorferi，这是螺旋体从节肢动物载体传播到哺乳动物宿主的关键步骤。
Outer surface protein C (OspC) is a differentially expressed major surface lipoprotein of Borrelia burgdorferi. ospC is swiftly upregulated when spirochetes leave the Ixodes scapularis tick gut, migrate to the salivary gland, and exit the arthropod vector. Here we show that OspC strongly binds to the tick salivary gland, suggesting a role for OspC in spirochete adherence to this tissue. In vivo studies using a murine model of Lyme borreliosis showed that while OspC F(ab)2 fragments did not influence either the viability of spirochetes or ospC gene expression, they did interfere with B. burgdorferi invasion of tick salivary glands. We then generated ospC knockout spirochetes in an infectious clone of B. burgdorferi and examined them within the vector. OspC-deficient or wild-type spirochetes persisted equally within the gut of unfed ticks and multiplied during the tick engorgement; however, unlike wild-type B. burgdorferi, the mutants were unable to invade salivary glands. Salivary gland colonization of OspC-deficient spirochetes was completely restored when this mutant was complemented in trans with a plasmid harboring the wild-type ospC gene. These studies conclusively demonstrate the importance of OspC in the invasion of tick salivary glands by B. burgdorferi, a critical step in the transmission of spirochetes from the arthropod vector to the mammalian host.