Constitutive Expression of Outer Surface Protein C Diminishes the Ability ofBorrelia burgdorferiTo Evade Specific Humoral Immunity

The Lyme disease spirocheteBorrelia burgdorferi reduces the expression of outer surface protein C (OspC) in response to the development of an anti-OspC humoral response, leading to the hypothesis that the ability to repress OspC expression is critical for the pathogen to proceed to chronic infection.B. burgdorferi was genetically modified to constitutively express OspC by introducing an extraospC copy fused with the borrelial flagellar gene (flaB ) promoter. Such a genetic modification did not reduce infectivity or pathogenicity in severe combined immunodeficiency mice but resulted in clearance of infection by passively transferred OspC antibody. Spirochetes with constitutiveospC expression were unable to establish chronic infections in immunocompetent mice unless they had undergone very destructive mutations in the introducedospC copy. Two escape mutants were identified; one had all 7 bp deleted between the putative ribosome-binding site and the start codon, ATG, causing a failure in translational initiation, and the other mutant had an insertion of 2 bp between nucleotides 315 and 316, resulting in a nonsense mutation at codon 108. Thus, the ability ofB. burgdorferi to repressospC expression during mammalian infection allows the pathogen to avoid clearance and to preserve the integrity of the important gene for subsequent utilization during its enzootic life cycle.