An analysis of expression of 137 lipoprotein genes on the course of murine infection revealed a two-step molecular adaptation by Borrelia burgdorferi, the Lyme disease spirochete. For the first step, regardless whether the initial inocula of B. burgdorferi expressed either all (cultured spirochetes) or less than 40 (host-adapted spirochetes) of the 137 lipoprotein genes, the spirochetes were modulated to transcribe 116 of the genes within 10 d after being introduced to the murine host. This step of adaptation was induced by the microenvironment of the host tissue. During the second step, which was forced by host immune selection pressure and occurred between 17 and 30 d after infection, B. burgdorferi down-regulated most of the lipoprotein genes and expressed less than 40 of the 137 genes. This novel adaptation mechanism could be a critical step for B. burgdorferi to proceed to chronic infection, as the pathogen would be cleared at the early stage of infection if the spirochetes failed to undergo this process.
Borrelia burgdorferi, the Lyme disease spirochete, persistently infects mammalian hosts despite the development of strong humoral responses directed against the pathogen. Here we describe a novel mechanism of immune evasion by B. burgdorferi. In immunocompetent mice, spirochetes that did not express ospC (the outer-surface protein C gene) were selected within 17 d after inoculation, concomitantly with the emergence of anti-OspC antibody. Spirochetes with no detectable OspC transcript that were isolated from immunocompetent mice reexpressed ospC after they were either cultured in vitro or transplanted to naive immunocompetent mice, but not in OspC-immunized mice. B. burgdorferi persistently expressed ospC in severe combined immune-deficient (SCID) mice. Passive immunization of B. burgdorferi–infected SCID mice with an anti-OspC monoclonal antibody selectively eliminated ospC-expressing spirochetes but did not clear the infection. OspC-expressing spirochetes reappeared in SCID mice after the anti-OspC antibody was eliminated. We submit that selection of surface-antigen nonexpressers is an immune evasion mechanism that contributes to spirochetal persistence.