Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice

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.