Wang G, Ojaimi C, Iyer R, Saksenberg V, McClain S A, Wormser G P, Schwartz I
Department of Biochemistry and Molecular Biology, Department of Medicine, New York Medical College, Valhalla, New York 10595, USA.
Infect Immun. 2001 Jul;69(7):4303-12. doi: 10.1128/IAI.69.7.4303-4312.2001.
Various genotypes of Borrelia burgdorferi sensu stricto have been previously identified among a large collection of isolates cultured from patients with Lyme disease in the United States. Furthermore, association of specific genotypes with hematogenous dissemination early in the disease course has been observed. The present study assessed kinetics of spirochete dissemination and disease severity in C3H/HeJ mice infected with two different genotypes of B. burgdorferi. Spirochete load in plasma and ear and other tissue samples of infected mice was measured by quantitative PCR, and these data were compared to those obtained by culture and histopathologic analysis. In mice infected with isolate BL206 (a type 1 strain), the peak number of spirochetes was observed in plasma between day 4 and 7, in heart and ear tissue on day 14, and in joints on day 28 postinoculation. There was a correlation between the peak number of spirochetes in plasma on day 4 or 7 and that in ear biopsy and joint specimens on day 14. By contrast, spirochete burdens in plasma of mice infected with isolate B356 (a type 3 strain) were 16- and 5-fold lower than those of BL206-infected mice on days 7 and 14 of infection, respectively. Similarly, approximately 6- and 13-fold fewer spirochetes were detected in the heart tissues of B356-infected mice compared to BL206-infected mice. Histopathologically, severe arthritis and aortitis were noted only in mice infected with isolate BL206. Spirochete dissemination and disease severity vary significantly in mice infected with distinct genotypes of B. burgdorferi, suggesting that genotypic differences in the infecting spirochetes play a key role in the pathogenesis and development of clinical disease.
先前在美国从莱姆病患者身上培养的大量分离菌株中已鉴定出多种狭义伯氏疏螺旋体基因型。此外,还观察到特定基因型与疾病早期血行播散之间的关联。本研究评估了感染两种不同基因型伯氏疏螺旋体的C3H/HeJ小鼠中螺旋体播散的动力学和疾病严重程度。通过定量PCR测量感染小鼠血浆、耳部和其他组织样本中的螺旋体载量,并将这些数据与通过培养和组织病理学分析获得的数据进行比较。在感染分离株BL206(1型菌株)的小鼠中,接种后第4至7天血浆中螺旋体数量达到峰值,第14天心脏和耳部组织中达到峰值,第28天关节中达到峰值。第4或7天血浆中螺旋体峰值数量与第14天耳部活检和关节标本中的螺旋体峰值数量之间存在相关性。相比之下,感染分离株B356(3型菌株)的小鼠在感染第7天和第14天血浆中的螺旋体载量分别比感染BL206的小鼠低16倍和5倍。同样,与感染BL206的小鼠相比,感染B356的小鼠心脏组织中检测到的螺旋体数量大约少6倍和13倍。组织病理学上,仅在感染分离株BL206的小鼠中观察到严重的关节炎和主动脉炎。感染不同基因型伯氏疏螺旋体小鼠的螺旋体播散和疾病严重程度差异显著,这表明感染螺旋体的基因型差异在临床疾病的发病机制和发展中起关键作用。