Narasimhan Sukanya, Caimano Melissa J, Liang Fang Ting, Santiago Felix, Laskowski Michelle, Philipp Mario T, Pachner Andrew R, Radolf Justin D, Fikrig Erol
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15953-8. doi: 10.1073/pnas.2432412100. Epub 2003 Dec 11.
Neurological symptoms are common manifestations of Lyme disease; however, the paucibacillary nature of the spirochete in this environment has precluded a molecular analysis of the spirochete in the CNS. We have now adapted differential expression analysis by using a custom-amplified library (DECAL) in conjunction with Borrelia burgdorferi whole-genome and subgenome arrays to examine in vivo gene expression by B. burgdorferi in a non-human primate (NHP) model of neuroborreliosis. The expression profile of B. burgdorferi was examined in the CNS and heart of steroid-treated and immunocompetent NHPs. Eighty-six chromosomal genes and 80 plasmid-encoded genes were expressed at similar levels in the CNS and heart tissue of both immunocompetent and steroid-treated NHPs. The expression of 66 chromosomal genes and 32 plasmid-encoded genes was increased in the CNS of both immunocompetent and steroid-treated NHPs. It is likely that the expression of these genes is governed by physiological factors specific to the CNS milieu. However, 83 chromosomal and 114 plasmid-encoded genes showed contrasting expression profiles in steroid-treated and immunocompetent NHPs. The effect of dexamethasone on the immune status of the host as well as on the host metabolic pathways could contribute to these differences in the B. burgdorferi transcriptome. Results obtained herein underscore the complex interplay of host factors on B. burgdorferi gene expression in vivo. The results provide a global snapshot of the spirochetal transcriptome in the CNS and should spur the design of experiments aimed at understanding the molecular basis of neuroborreliosis.
神经症状是莱姆病的常见表现;然而,这种环境中螺旋体的少菌性质使得无法对中枢神经系统中的螺旋体进行分子分析。我们现在通过使用定制扩增文库(DECAL)结合伯氏疏螺旋体全基因组和亚基因组阵列来调整差异表达分析,以研究伯氏疏螺旋体在神经型莱姆病非人灵长类动物(NHP)模型中的体内基因表达。在接受类固醇治疗和具有免疫活性的NHP的中枢神经系统和心脏中检查了伯氏疏螺旋体的表达谱。在具有免疫活性和接受类固醇治疗的NHP的中枢神经系统和心脏组织中,86个染色体基因和80个质粒编码基因的表达水平相似。在具有免疫活性和接受类固醇治疗的NHP的中枢神经系统中,66个染色体基因和32个质粒编码基因的表达增加。这些基因的表达可能受中枢神经系统环境特有的生理因素控制。然而,83个染色体基因和114个质粒编码基因在接受类固醇治疗和具有免疫活性的NHP中表现出相反的表达谱。地塞米松对宿主免疫状态以及宿主代谢途径的影响可能导致伯氏疏螺旋体转录组的这些差异。本文获得的结果强调了宿主因素在体内对伯氏疏螺旋体基因表达的复杂相互作用。这些结果提供了中枢神经系统中螺旋体转录组的全局快照,应该会促使开展旨在了解神经型莱姆病分子基础的实验设计。