YebC Modulates OspC and VlsE Inverse Regulation and VlsE Expression in Persistent Lyme Disease

Abstract

Background & Hypothesis: Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common vector-borne infectious disease in the United States. Although easily treated with antibiotics, undiagnosed cases may develop into persistent infections with complications including Lyme carditis, neuroborreliosis, & arthritis. VlsE antigen variation is one of the major mechanisms employed by B. burgdorferi to establish persistent infection. We hypothesize that YebC modulates VlsE expression and antigen variation, enabling the shift from acute to persistent infection.

Materials & Methods: C3H/HeN or C3H/SCID mice were infected with the B. burgdorferi strain 5A4NP1, yebC mutant, and yebC complement at a dose of 10⁵ or 10⁶ spirochetes. Mice were sacrificed at days 7, 30, 60, and 90 post-infection and tissue samples were subjected to RNA and DNA extraction.

Results: YebC levels were closely associated with the upregulation of vlsE and the downregulation of ospC in vitro and in vivo. The yebC mutant displayed loss of infectivity in C3H/HeN mice, and reduced VlsE antigen variation.

Conclusion & Impact: This data demonstrates that YebC of B burgdorferi can regulate the frequency of vlsE recombination and modulates the inverse regulation of OspC and VlsE. This new factor may serve as an avenue for developing drugs which can target vlsE recombination to combat complications of persistent Lyme disease.