Microbiology and Pathogenesis Activity, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
PLoS One. 2011 May 3;6(5):e19536. doi: 10.1371/journal.pone.0019536.
Borrelia burgdorferi, the causative agent of Lyme borreliosis, is transmitted to humans from the bite of Ixodes spp. ticks. During the borrelial tick-to-mammal life cycle, B. burgdorferi must adapt to many environmental changes by regulating several genes, including bba64. Our laboratory recently demonstrated that the bba64 gene product is necessary for mouse infectivity when B. burgdorferi is transmitted by an infected tick bite, but not via needle inoculation. In this study we investigated the phenotypic properties of a bba64 mutant strain, including 1) replication during tick engorgement, 2) migration into the nymphal salivary glands, 3) host transmission, and 4) susceptibility to the MyD88-dependent innate immune response. Results revealed that the bba64 mutant's attenuated infectivity by tick bite was not due to a growth defect inside an actively feeding nymphal tick, or failure to invade the salivary glands. These findings suggested there was either a lack of spirochete transmission to the host dermis or increased susceptibility to the host's innate immune response. Further experiments showed the bba64 mutant was not culturable from mouse skin taken at the nymphal bite site and was unable to establish infection in MyD88-deficient mice via tick infestation. Collectively, the results of this study indicate that BBA64 functions at the salivary gland-to-host delivery interface of vector transmission and is not involved in resistance to MyD88-mediated innate immunity.
伯氏疏螺旋体（Borrelia burgdorferi）是莱姆病的病原体，通过硬蜱属（Ixodes spp.）的叮咬传播给人类。在伯氏疏螺旋体从蜱到哺乳动物的生命周期中，必须通过调节包括 bba64 在内的几个基因来适应许多环境变化。我们实验室最近证明，当伯氏疏螺旋体通过受感染的蜱叮咬传播而不是通过针接种传播时，bba64 基因产物对于小鼠感染性是必需的。在这项研究中，我们研究了 bba64 突变株的表型特性，包括 1）在蜱饱食期间的复制，2）迁移到若虫唾液腺，3）宿主传播，和 4）对 MyD88 依赖性先天免疫反应的敏感性。结果表明，bba64 突变体通过蜱叮咬的感染性减弱不是由于在活跃进食的若虫蜱内的生长缺陷，或未能侵入唾液腺。这些发现表明，要么是螺旋体向宿主真皮的传播缺乏，要么是对宿主先天免疫反应的敏感性增加。进一步的实验表明，bba64 突变体不能从若虫叮咬部位的小鼠皮肤中培养出来，并且不能通过蜱感染在 MyD88 缺陷型小鼠中建立感染。总的来说，这项研究的结果表明 BBA64 在媒介传播的唾液腺到宿主传递界面发挥作用，并且不参与对 MyD88 介导的先天免疫的抵抗。
