Departments of Microbiology & Molecular Genetics, Medicine, and Ecology and Evolutionary Biology, University of California, Irvine, CA, USA.
mBio. 2012 Dec 4;3(6):e00434-12. doi: 10.1128/mBio.00434-12.
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.
Humans are dead-end hosts for Borrelia agents of Lyme disease (LD), and, thus, irrelevant for the pathogens' maintenance. Many reports of human cases and laboratory mouse infections exist, but less is known about infection and immunity in natural reservoirs, such as the rodent Peromyscus leucopus. We observed that high- and low-prevalence strains of Borrelia burgdorferi were capable of infecting P. leucopus but elicited different patterns of antibody responses. Antibody reactivities to the VlsE protein were as type-specific as previously characterized reactivities to serotype-defining OspC proteins. In addition, the low-prevalence strains lacked full-length genes for two proteins that (i) are encoded by a virulence-associated plasmid in some high-prevalence strains and (ii) LD patients and field-captured rodents commonly have antibodies to. Immune selection against these genes may have led to null phenotype lineages that can infect otherwise immune hosts but at the cost of reduced fitness and lower prevalence.
啮齿动物白足鼠是莱姆病病原体伯氏疏螺旋体的主要天然宿主，也是其传播媒介肩突硬蜱的宿主。在美国东北部的不同地点，10 到 15 种伯氏疏螺旋体菌株以不同的流行率共存于蜱种群中。我们想知道高或低流行率的代表性菌株在感染白足鼠方面是否存在差异。在对每组用 6 个分离株进行 5 周的实验性感染后，通过定量 PCR 测量组织中的细菌分布和负荷，并通过免疫印迹和蛋白质微阵列评估针对伯氏疏螺旋体的抗体。所有动物组均在关节、耳朵、尾巴和心脏中感染，但感染低流行率菌株的动物的螺旋体总负荷较低。无论感染的分离株如何，动物对全细胞、FlaB、BmpA 和 DbpB 蛋白以及血清型定义 OspC 蛋白保守 N 端区域的抗体水平均相似。但针对全长 OspC 以及质粒编码的 VlsE、BBK07 和 BBK12 蛋白存在菌株特异性抗体反应。对额外的 VlsE 基因进行测序显示，一些菌株对的基因存在很大的多样性，但其他菌株的序列几乎相同，而其他菌株在 ospC 等位基因上存在差异。全长度 bbk07 和 bbk12 基因的存在或缺失解释了抗体反应的差异。我们提出，对于伯氏疏螺旋体，在储主物种中存在（i）序列多样性，如 OspC 和 VlsE，以及（ii）多态性的存在或缺失，如 BBK07 和 BBK12，这是选择的结果。
莱姆病（LD）的伯氏疏螺旋体病原体的人类是死胡同宿主，因此与病原体的维持无关。有许多关于人类病例和实验室小鼠感染的报告，但对自然储主（如啮齿动物白足鼠）的感染和免疫知之甚少。我们观察到，高和低流行率的伯氏疏螺旋体菌株能够感染白足鼠，但引起不同的抗体反应模式。针对 VlsE 蛋白的抗体反应与先前针对血清型定义 OspC 蛋白的反应一样具有血清型特异性。此外，低流行率菌株缺乏两个蛋白质的全长基因，这两个蛋白质（i）在一些高流行率菌株中由毒力相关质粒编码，（ii）LD 患者和野外捕获的啮齿动物通常对其有抗体。针对这些基因的免疫选择可能导致缺失表型谱系，这些谱系能够感染原本免疫的宿主，但代价是降低适应性和降低流行率。
