Persistence of Borrelia burgdorferi following antibiotic treatment in mice

Abstract

The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis. Mice were treated with ceftriaxone or saline solution for 1 month, commencing during the early (3 weeks) or chronic (4 months) stages of infection with Borrelia burgdorferi. Tissues from mice were tested for infection by culture, PCR, xenodiagnosis, and transplantation of allografts at 1 and 3 months after completion of treatment. In addition, tissues were examined for the presence of spirochetes by immunohistochemistry. In contrast to saline solution-treated mice, mice treated with antibiotic were consistently culture negative, but tissues from some of the mice remained PCR positive, and spirochetes could be visualized in collagen-rich tissues. Furthermore, when some of the antibiotic-treated mice were fed on by Ixodes scapularis ticks (xenodiagnosis), spirochetes were acquired by the ticks, as determined based upon PCR results, and ticks from those cohorts transmitted spirochetes to naïve SCID mice, which became PCR positive but culture negative. Results indicated that following antibiotic treatment, mice remained infected with nondividing but infectious spirochetes, particularly when antibiotic treatment was commenced during the chronic stage of infection.

Figures

FIG. 1.

Immunohistochemical labeling of multiple B. burgdorferi spirochetes (arrows) in ligament tissue of the tibiotarsal joint of a saline solution-treated (control) mouse (A) and of a single spirochete (arrow) in ligament tissue of the tibiotarsal joint of a ceftriaxone-treated mouse (B). Both images are from mice treated with saline solution (A) or ceftriaxone (B) at 4 months after inoculation with B. burgdorferi and subjected to necropsy 1 month after completion of treatment.

FIG. 2.

B. burgdorferi immunoglobulin G ELISA titers (mean reciprocal dilution ± SD) for mice treated with saline solution or ceftriaxone for 1 month, commencing at 4 months after infection. The dotted box (Rx) indicates the interval of treatment relative to the stage of infection.