mBio：揭示莱姆病研究新线索

刊登在2012任何12月4日的国际杂志mBio上的一篇研究报告中，来自加州大学的研究者揭示了，引发莱姆病相关细菌的一些线索，旨在帮助研究者开发出新型的降低感染的技术。这项研究中，研究者揭示了白足鼠（伯氏疏螺旋体的宿主）的免疫系统对于不同细菌菌株可以产生不同的免疫反应，这或许帮助研究者开发抵御感染的新方法。

莱姆病仅仅在美国被发现，在过去40年里，有25，000人患病，给社会和个人造成严重的经济负担。本文中，研究者试图去理解15种不同的伯氏疏螺旋体的流行度为何不同，在莱姆病常常发生的几个区域，大部分的白足鼠也受到了伯氏疏螺旋体的感染。白足鼠不像人类和正常鼠类，当其感染伯氏疏螺旋体后，并不会发病。

实验室条件下，研究者将白足鼠暴露于伯氏疏螺旋体下，研究其被感染的过程，所有的伯氏疏螺旋体都会感染白足鼠，但是有一些菌株却会设法在白足鼠多种组织中生长，以变得细菌浓度加大。结果显示，白足鼠的免疫反应越强烈，在其组织中发现的细菌越少，反之亦然。更为重要的是，在白足鼠组织中高浓度存在的菌株也是较为流行的菌株。

当针对单一的伯氏疏螺旋体蛋白产生免疫反应的时候，研究者发现了一种复杂的相互作用，白足鼠可以对单一细菌菌株存在的不同类型的蛋白质产生不同程度的反应，这就帮助我们解释为何在自然界中伯氏疏螺旋体会出现单一多样性。

一旦针对白足鼠的疫苗研发出来，其就可以用于暴露在免疫过的小鼠中进行选择性检测了。这项研究为我们了解莱姆病以及伯氏疏螺旋体的感染，以及新型疫苗的开发提供了新的思路和建议。

doi:10.1128/​mBio.00434-12
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Experimental Infections of the Reservoir Species Peromyscus leucopus with Diverse Strains of Borrelia burgdorferi, a Lyme Disease Agent

Elisabeth Baum, Fong Hue, and Alan G. Barbour

The rodent Peromyscus leucopus is a major natural reservoir for the Lyme disease agent Borrelia burgdorferi and a host for its vector Ixodes scapularis. At various locations in northeastern United States 10 to 15 B. burgdorferi strains coexist at different prevalences in tick populations. We asked whether representative strains of high or low prevalence differed in their infections of P. leucopus. After 5 weeks of experimental infection of groups with each of 6 isolates, distributions and burdens of bacteria in tissues were measured by quantitative PCR, and antibodies to B. burgdorferi were evaluated by immunoblotting and protein microarray. All groups of animals were infected in their joints, ears, tails, and hearts, but overall spirochete burdens were lower in animals infected with low-prevalence strains. Animals were similar regardless of the infecting isolate in their levels of antibodies to whole cells, FlaB, BmpA, and DbpB proteins, and the conserved N-terminal region of the serotype-defining OspC proteins. But there were strain-specific antibody responses to full-length OspC and to plasmid-encoded VlsE, BBK07, and BBK12 proteins. Sequencing of additional VlsE genes revealed substantial diversity within some pairs of strains but near-identical sequences within other pairs, which otherwise differed in their ospC alleles. The presence or absence of full-length bbk07 and bbk12 genes accounted for the differences in antibody responses. We propose that for B. burgdorferi, there is selection in reservoir species for (i) sequence diversity, as for OspC and VlsE, and (ii) the presence or absence of polymorphisms, as for BBK07 and BBK12.