| The causative agent of Lyme disease, Borrelia burgdorferi, is transmitted to humans and other vertebrate animals through the bites of infected Ixodes ticks. As the bacterium persistently infects a wide variety of vertebrate hosts, it must coordinate the expression of numerous genes and proteins beneficial for persistence in these hosts. B. burgdorferi proteins associated with vertebrate infection that I have examined are the Erp, OspC, EppA, and BapA proteins. Through the course of this dissertation work, I have demonstrated that Erp protein expression is regulated during the natural tick-mammal infectious cycle. Results of my studies suggest that Erp proteins play a role in both the acquisition and transmission of B. burgdorferi by its tick vector. In addition, infected mice mount a rapid IgM antibody response to Erp and OspC proteins which is followed by a robust IgG response that persists for at least eleven months of infection. These data suggest continued exposure of these proteins to the host immune system. Infected Lyme disease patients produce antibodies that recognize 19 and 60 KDa B. burgdorferi proteins, which are the sizes of the ErpA and ErpB proteins of strain B31. While I found that bacteria cultured from these patients contain genes similar to erpA and erpB, other studies in our lab demonstrated that only a subset of patients produce antibodies that recognize the B31 Erps. I conclude that ErpA and ErpB are not the 19 and 60 KDa immunodiagnostic antigens. I have discovered that B. burgdorferi strain B31 subculture RML contains a novel 9 kb circular plasmid, dubbed cp9-2. I have characterized this plasmid, which bears an allele of eppA, designated eppA2. Finally, I have shown that a majority of examined B. burgdorferi strains contain eppA and bapA genes. While the predicted EppA proteins are antigenic but vary widely between different strains, BapA is very well conserved among B. burgdorferi strains but is not very antigenic. Data from these and other studies suggest important roles for BapA and EppA during the B. burgdorferi infectious cycle. |
