The Lyme disease spirochete Borrelia 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 extra
ospC 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 constitutive
ospC expression were unable to establish
chronic infections in immunocompetent mice unless they had undergone very destructive mutations in the introduced
ospC 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 of B. burgdorferi to repress
ospC 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.