Cadavid D, Thomas D D, Crawley R, Barbour A G
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284.
J Exp Med. 1994 Feb 1;179(2):631-42. doi: 10.1084/jem.179.2.631.
During persistent infection of scid mice with Borrelia turicatae, an agent of relapsing fever and neuroborreliosis, there was variation in the surface proteins the bacteria expressed and in disease manifestations over time. Two serotypes, A and B, were isolated from the mice, cloned by limiting dilution, and further characterized. The only discernible difference between the two variants was in the size of the major surface protein they expressed: serotype A had a variable major protein (Vmp) of 23,000, and serotype B had a Vmp of 20,000. When other scid mice were inoculated with clonal populations of A and B, the infections were similar with respect to onset and degree of spirochetemia, involvement of the eye and heart, and occurrence of a peripheral vestibular disorder. However, there were differences between the serotypes in other respects: (a) serotype B but not A caused reddened and significantly enlarged joints, markedly impaired performance on a walking bar, and severe arthritis by histologic examination; (b) serotype A but not B invaded the central nervous system during early infection; and (c) serotype A penetrated monolayers of human umbilical vein endothelial cells more readily than did serotype B. The combination of arthritis, myocarditis, and neurologic disease resembled human Lyme borreliosis. The findings indicate that differences in disease expression are determined by variable surface proteins of the bacterium and that scid mouse infections with B. turicatae provide a model for the study of the pathogenesis of Lyme borreliosis and other persistent spirochetal diseases.
在用复发性发热和神经莱姆病病原体土拉疏螺旋体持续感染重度联合免疫缺陷（scid）小鼠的过程中，随着时间推移，细菌表达的表面蛋白以及疾病表现存在差异。从这些小鼠中分离出A和B两种血清型，通过有限稀释法进行克隆，并进一步鉴定。这两种变体之间唯一可辨别的差异在于它们所表达的主要表面蛋白的大小：血清型A的可变主要蛋白（Vmp）为23,000，血清型B的Vmp为20,000。当用A和B的克隆群体接种其他scid小鼠时，感染在螺旋体血症的发作和程度、眼睛和心脏的受累情况以及外周前庭障碍的发生方面相似。然而，血清型在其他方面存在差异：（a）血清型B而非A导致关节发红且明显肿大，在行走杆上的表现明显受损，组织学检查显示有严重关节炎；（b）血清型A而非B在早期感染期间侵入中枢神经系统；（c）血清型A比血清型B更容易穿透人脐静脉内皮细胞单层。关节炎、心肌炎和神经疾病的组合类似于人类莱姆病。这些发现表明，疾病表现的差异由细菌的可变表面蛋白决定，并且土拉疏螺旋体感染scid小鼠为研究莱姆病和其他持续性螺旋体疾病的发病机制提供了一个模型。
