NEW ANIMAL-MODEL FOR STUDYING LYME-DISEASE SPIROCHETES IN A MAMMALIANHOST-ADAPTED STATE

There is now substantial evidence that Borrelia burgdorferi, the Lyme disease spirochete, undergoes major alterations in antigenic compositi on as it cycles between its arthropod and mammalian hosts. In this rep ort, we cultivated B. burgdorferi 297 within dialysis membrane chamber s implanted into the peritoneal cavities of rats to induce antigenic c hanges similar to those which occur during mammalian infection. Chambe r-grown spirochetes, which remained fully virulent, did not express ei ther outer surface protein A or Lp6.6, lipoproteins known to be downre gulated after mammalian infection. However, they did, express p21, a w ell characterized outer surface protein E homologue, which is selectiv ely expressed during infection. SDS-PAGE, two-dimensional gel electrop horesis, and immunoblot analysis revealed that chamber-grown borreliae also expressed uncharacterized proteins not expressed by in vitro-cul tivated spirochetes; reactivity with sera from mice chronically infect ed with B. burgdorferi 297 confirmed that many of these novel proteins are selectively expressed during experimental murine infection. Final ly, we used differential display RT-PCR to identify transcripts of oth er differentially expressed B. burgdorferi genes. One gene (2.9-7lpB) identified with this technique belongs to a family of genes located on homologous 32- and 18-kb circular plasmids, The lipoprotein encoded b y 2.9-7lpB was shown to be selectively expressed by chamber-grown spir ochetes and by spirochetes during experimental infection. Cultivation of B. burgdorferi in rat peritoneal implants represents a novel system for studying Lyme disease spirochetes in a mammalian host-adapted sta te.