Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
Infect Immun. 2011 Mar;79(3):1208-17. doi: 10.1128/IAI.01156-10. Epub 2010 Dec 20.
The genome of Borrelia burgdorferi, the causative agent of Lyme disease, is comprised of a large linear chromosome and numerous smaller linear and circular plasmids. B. burgdorferi exhibits substantial genomic variation, and previous studies revealed genotype-specific variation at the right chromosomal telomere. A correlation has also been established between genotype and invasiveness. The correlation between chromosome length and genotype and between genotype and invasiveness suggested that a gene(s) at the right chromosome telomere may be required for virulence. Of particular interest was bb0844, an RpoS-regulated gene at the right telomere, the expression of which is induced when the spirochete undergoes adaptation to the mammalian host. The structure of the right chromosomal telomere was examined in 53 B. burgdorferi clinical isolates of various genotypes. Four distinct patterns were observed for bb0844: (i) chromosomal localization, (ii) plasmid localization, (iii) presence on both chromosome and plasmid, and (iv) complete absence. These patterns correlated with the B. burgdorferi genotype. On the basis of available sequence data, we propose a mechanism for the genomic rearrangements that accounts for the variability in bb0844 genomic localization. To further explore the role of BB0844 in the spirochete life cycle, a bb0844 deletion mutant was constructed by allelic exchange, and the viability of wild-type and bb0844 deletion mutants was examined in an experimental mouse-tick infection model. The bb0844 mutant was fully infectious in C3H/HeJ mice by either needle inoculation or tick transmission with B. burgdorferi-infected Ixodes scapularis larvae. Naïve larval ticks acquired both wild-type and mutant spirochetes with equal efficiency from B. burgdorferi-infected mice. The results demonstrate that BB0844 is not required for spirochete viability, pathogenicity, or maintenance in the tick vector or the mammalian host. At present, a defined role for BB0844 in B. burgdorferi cannot be ascertained.
伯氏疏螺旋体的基因组由一条大的线性染色体和许多较小的线性和圆形质粒组成。伯氏疏螺旋体表现出大量的基因组变异，先前的研究表明在右染色体端粒处存在基因型特异性变异。还建立了基因型与侵袭性之间的相关性。染色体长度与基因型之间以及基因型与侵袭性之间的相关性表明，右染色体端粒处的一个（或多个）基因可能是毒力所必需的。特别有趣的是 bb0844，它是右端粒处受 RpoS 调控的基因，当螺旋体适应哺乳动物宿主时，其表达会被诱导。在各种基因型的 53 株伯氏疏螺旋体临床分离株中检查了右染色体端粒的结构。观察到 bb0844 有四种不同的模式：（i）染色体定位，（ii）质粒定位，（iii）染色体和质粒上均存在，以及（iv）完全缺失。这些模式与伯氏疏螺旋体的基因型相关。根据现有序列数据，我们提出了一种基因组重排的机制，该机制解释了 bb0844 基因组定位的可变性。为了进一步探索 BB0844 在螺旋体生命周期中的作用，通过等位基因交换构建了 bb0844 缺失突变体，并在实验性小鼠-蜱感染模型中检查了野生型和 bb0844 缺失突变体的活力。bb0844 突变体通过针接种或感染 B. burgdorferi 的 Ixodes scapularis 幼虫传播在 C3H/HeJ 小鼠中具有完全感染力。幼稚的幼虫蜱从感染 B. burgdorferi 的小鼠中以相同的效率获得野生型和突变型螺旋体。结果表明，BB0844 对于螺旋体的活力、致病性或在蜱载体或哺乳动物宿主中的维持都不是必需的。目前，尚不能确定 BB0844 在伯氏疏螺旋体中的明确作用。
