OspC-independent infection and dissemination by host-adapted Borrelia burgdorferi.
Borrelia burgdorferi OspC is required for the spirochete to establish infection in a mammal by tick transmission or needle inoculation. After a brief essential period, the protein no longer is required and the gene can be shut off. Using a system in which spirochetes contain only an unstable wild-type copy of the ospC gene, we can obtain mice persistently infected with bacteria lacking OspC. We implanted pieces of infected mouse skin subcutaneously in naïve mice, using donors carrying wild-type or ospC mutant spirochetes, and found that both could infect mice by this method, with similar numbers of wild-type or ospC mutant spirochetes disseminated throughout the tissues of recipient mice. Recipient mouse immune responses to tissue transfer-mediated infection with wild-type or ospC mutant spirochetes were similar. These experiments demonstrate that mammalian host-adapted spirochetes can infect and disseminate in mice in the absence of OspC, thereby circumventing this hallmark of tick-derived or in vitro-grown spirochetes. We propose a model in which OspC is one of a succession of functionally equivalent, essential proteins that are synthesized at different stages of mammalian infection. In this model, another protein uniquely present on host-adapted spirochetes performs the same essential function initially fulfilled by OspC. The strict temporal control of B. burgdorferi outer surface protein gene expression may reflect immunological constraints rather than distinct functions.
Tilly
Kit
K
Laboratory of Zoonotic Pathogens, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA.
Bestor
Aaron
A
Dulebohn
Daniel P
DP
Rosa
Patricia A
PA
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D001899:Borrelia Infections / Q000382:microbiology* / Q000635:transmission*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008954:Models, Biological
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C079616:OspC protein