Bacterial Heterogeneity Is a Requirement for Host Superinfection by the Lyme Disease Spirochete

In nature, mixed Borrelia burgdorferi infections are common and possibly can be acquired by either superinfection or coinfection. Superinfection by heterologous B. burgdorferi strains has been established experimentally, although the ability of homologous B. burgdorferi clones to superinfect a host has not been studied in detail. Information regarding any potential immune barriers to secondary infection also currently is unavailable. In the present study, the ability to superinfect various mouse models by homologous wild-type clones was examined and compared to superinfection by heterologous strains. To assess the ability of homologous B. burgdorferi clones to successfully superinfect a mouse host, primary-and secondary-infecting spirochetes were recovered via in vitro cultivation of collected blood or tissue samples. This was accomplished by generating two different antibiotic-resistant versions of the wild-type B31-A3 clone in order to distinguish superinfecting B. burgdorferi from primary-infecting spirochetes. The data demonstrate an inability of homologous B. burgdorferi to superinfect immunocompetent mice as opposed to heterologous strains. Attempts to superinfect different types of immunodeficient mice with homologous B. burgdorferi indicate that the murine innate immune system represents a major barrier to intrastrain superinfection. Consequently, the possibility of innate immunity as a driving force for B. burgdorferi heterogeneity during the enzootic cycle is discussed.