Complement-mediated serum sensitivity among spirochetes that cause Lyme disease

Borrelia burgdorferi-related isolates were tested for their sensitivity to normal human serum (NHS) and their ability to activate complement, By dark-field microscopy, electron microscopy, and subsurface plating, it was shown that exposure of a Borrelia garinii isolate to 10% or more NHS resulted in immobilization, blebbing, and killing of the spirochetes. These effects were mediated by complement, since they were not seen after heat treatment of NHS, in the presence of EDTA, or in an agammaglobulinemic serum, All seven B. garinii type 5 or 6 and all four VS116iM19 strains were serum sensitive, whereas all eight Borrelia afzelii, five of eight B. garinii type 4, and three of seven B. burgdorferi sensu stricto isolates were serum resistant, The other isolates were partially serum sensitive, Four serum-sensitive B. garinii isolates had been isolated from human cerebrospinal fluid, Most likely, activation of both the alternative pathway and the classical pathway of complement was involved, since bactericidal activity was diminished in properdin-deficient sera as well as in a C1q-depleted serum and in a C4-deficient serum, Bactericidal activity could be restored when a serum lacking Clq or C4 was mixed with a properdin-deficient serum, Isolates with various genetic backgrounds were equally able to activate C3 as measured by enzyme-linked immunosorbent assay, In the presence of Mg-EGTA, C3 mas activated by all isolates after exposure to greater than or equal to 10% NBS. This study shows that B. burgdorferi-related spirochetes can be either serum sensitive or serum resistant in vitro and that this characteristic is associated with their genetic background.